Academic Journal

The Master Regulator Spo0A Integrates DNA Sequence and Shape to Regulate the Sporulation Kinase Gene kinA in Bacillus subtilis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: The Master Regulator Spo0A Integrates DNA Sequence and Shape to Regulate the Sporulation Kinase Gene kinA in Bacillus subtilis.
Συγγραφείς: Zahid SH; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA., Zarazúa-Osorio B; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA., Escobedo R; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA., Ullah S; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA., Dona SKK; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA., Fujita M; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
Πηγή: Molecular microbiology [Mol Microbiol] 2026 Oct; Vol. 126 (4), pp. 359-378. Date of Electronic Publication: 2026 Jul 28.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8712028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2958 (Electronic) Linking ISSN: 0950382X NLM ISO Abbreviation: Mol Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: Oxford, OX ; Boston, MA : Blackwell Scientific Publications, c1987-
Ιατρικοί όροι (MeSH): Bacillus subtilis*/genetics , Bacillus subtilis*/metabolism , Bacterial Proteins*/genetics , Bacterial Proteins*/metabolism , Protein Kinases*/genetics , Protein Kinases*/metabolism , Transcription Factors*/metabolism , Transcription Factors*/genetics, Gene Expression Regulation, Bacterial/genetics ; Spores, Bacterial/genetics ; Spores, Bacterial/metabolism ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Promoter Regions, Genetic ; Phosphorylation ; Transcription, Genetic
Περίληψη: Sporulation in starved Bacillus subtilis depends on precise control of kinA, which encodes the major phosphorelay kinase that generates the threshold level of phosphorylated Spo0A (Spo0A~P) required for entry into sporulation. Here, we define the regulatory logic that shapes kinA expression and uncover structural features that influence Spo0A~P recruitment. First, we show that the kinA promoter integrates positive and negative Spo0A~P inputs through a composite three-site 0A-box architecture. Distinct affinities and cooperative interactions among the three sites generate a controlled output in which activating and repressive inputs are balanced during starvation, maintaining basal-to-moderate kinA transcription. Second, we identify intrinsic DNA bending as a sequence-independent mechanism that enhances Spo0A~P engagement, promoting low-specificity interactions that may contribute to transcriptional regulation and more broadly chromosome organization. Finally, we show that both the kinA promoter and KinA protein domains diverge between pathogenic and nonpathogenic Bacillus species, reflecting niche-specific evolutionary pressures on sporulation initiation. Together, these findings support an integrated model in which promoter architecture and DNA shape collectively tune Spo0A~P dependent regulation of kinA.
(© 2026 John Wiley & Sons Ltd.)
References: Ben‐Yehuda, S., D. Z. Rudner, and R. Losick. 2003. “RacA, a Bacterial Protein That Anchors Chromosomes to the Cell Poles.” Science 299: 532–536.
Bossi, L., and D. M. Smith. 1984. “Conformational Change in the DNA Associated With an Unusual Promoter Mutation in a tRNA Operon of Salmonella.” Cell 39: 643–652.
Burbulys, D., K. A. Trach, and J. A. Hoch. 1991. “Initiation of Sporulation in B. subtilis Is Controlled by a Multicomponent Phosphorelay.” Cell 64: 545–552.
Carniol, K., P. Eichenberger, and R. Losick. 2004. “A Threshold Mechanism Governing Activation of the Developmental Regulatory Protein Sigma F in Bacillus subtilis.” Journal of Biological Chemistry 279: 14860–14870.
Chastanet, A., and R. Losick. 2011. “Just‐In‐Time Control of Spo0A Synthesis in Bacillus subtilis by Multiple Regulatory Mechanisms.” Journal of Bacteriology 193: 6366–6374.
Chen, Z., P. Srivastava, B. Zarazua‐Osorio, A. Marathe, M. Fujita, and O. A. Igoshin. 2022. “Bacillus subtilis Histidine Kinase KinC Activates Biofilm Formation by Controlling Heterogeneity of Single‐Cell Responses.” MBio 13: e0169421.
Devi, S. N., B. Kiehler, L. Haggett, and M. Fujita. 2015. “Evidence That Autophosphorylation of the Major Sporulation Kinase in Bacillus subtilis Is Able to Occur in Trans.” Journal of Bacteriology 197: 2675–2684.
Devi, S. N., M. Vishnoi, B. Kiehler, L. Haggett, and M. Fujita. 2015. “In Vivo Functional Characterization of the Transmembrane Histidine Kinase KinC in Bacillus subtilis.” Microbiology 161: 1092–1104.
Dutta, R., L. Qin, and M. Inouye. 1999. “Histidine Kinases: Diversity of Domain Organization.” Molecular Microbiology 34: 633–640.
Ellermeier, C. D., E. C. Hobbs, J. E. Gonzalez‐Pastor, and R. Losick. 2006. “A Three‐Protein Signaling Pathway Governing Immunity to a Bacterial Cannibalism Toxin.” Cell 124: 549–559.
Elufisan, T. O., and N. M. Rosas‐Garcia. 2025. “Whole Genome Sequence Analysis of Pigmented Bacillus Inaquosorum LBA001 Revealed Biosynthetic Gene Clusters for a Variety of Secondary Metabolites.” Antonie Van Leeuwenhoek 118: 107.
Errington, J. 2003. “Regulation of Endospore Formation in Bacillus subtilis.” Nature Reviews. Microbiology 1: 117–126.
Eswaramoorthy, P., A. Dravis, S. N. Devi, M. Vishnoi, H. A. Dao, and M. Fujita. 2011. “Expression Level of a Chimeric Kinase Governs Entry Into Sporulation in Bacillus subtilis.” Journal of Bacteriology 193: 6113–6122.
Eswaramoorthy, P., D. Duan, J. Dinh, A. Dravis, S. N. Devi, and M. Fujita. 2010. “The Threshold Level of the Sensor Histidine Kinase KinA Governs Entry Into Sporulation in Bacillus subtilis.” Journal of Bacteriology 192: 3870–3882.
Eswaramoorthy, P., and M. Fujita. 2010. “Systematic Domain Deletion Analysis of the Major Sporulation Kinase in Bacillus subtilis.” Journal of Bacteriology 192: 1744–1748.
Eswaramoorthy, P., T. Guo, and M. Fujita. 2009. “In Vivo Domain‐Based Functional Analysis of the Major Sporulation Sensor Kinase, KinA, in Bacillus subtilis.” Journal of Bacteriology 191: 5358–5368.
Fihn, C. A., and E. E. Carlson. 2021. “Targeting a Highly Conserved Domain in Bacterial Histidine Kinases to Generate Inhibitors With Broad Spectrum Activity.” Current Opinion in Microbiology 61: 107–114.
Fujita, M. 2000. “Temporal and Selective Association of Multiple Sigma Factors With RNA Polymerase During Sporulation in Bacillus subtilis.” Genes to Cells 5: 79–88.
Fujita, M., J. E. Gonzalez‐Pastor, and R. Losick. 2005. “High‐ and Low‐Threshold Genes in the Spo0A Regulon of Bacillus subtilis.” Journal of Bacteriology 187: 1357–1368.
Fujita, M., and R. Losick. 2003. “The Master Regulator for Entry Into Sporulation in Bacillus subtilis Becomes a Cell‐Specific Transcription Factor After Asymmetric Division.” Genes & Development 17: 1166–1174.
Fujita, M., and R. Losick. 2005. “Evidence That Entry Into Sporulation in Bacillus subtilis Is Governed by a Gradual Increase in the Level and Activity of the Master Regulator Spo0A.” Genes & Development 19: 2236–2244.
Fujita, M., and Y. Sadaie. 1998a. “Feedback Loops Involving Spo0A and AbrB in In Vitro Transcription of the Genes Involved in the Initiation of Sporulation in Bacillus subtilis.” Journal of Biochemistry 124: 98–104.
Fujita, M., and Y. Sadaie. 1998b. “Promoter Selectivity of the Bacillus subtilis RNA Polymerase sigmaA and sigmaH Holoenzymes.” Journal of Biochemistry 124: 89–97.
Grossman, A. D. 1995. “Genetic Networks Controlling the Initiation of Sporulation and the Development of Genetic Competence in Bacillus subtilis.” Annual Review of Genetics 29: 477–508.
Gupta, R. S., S. Patel, N. Saini, and S. Chen. 2020. “Robust Demarcation of 17 Distinct Bacillus Species Clades, Proposed as Novel Bacillaceae Genera, by Phylogenomics and Comparative Genomic Analyses: Description of Robertmurraya kyonggiensis sp. Nov. and Proposal for an Emended Genus Bacillus Limiting It Only to the Members of the Subtilis and Cereus Clades of Species.” International Journal of Systematic and Evolutionary Microbiology 70: 5753–5798.
Haggett, L., A. Bhasin, P. Srivastava, and M. Fujita. 2018. “A Revised Model for the Control of Fatty Acid Synthesis by Master Regulator Spo0A in Bacillus subtilis.” Molecular Microbiology 108: 424–442.
Haran, T. E., and U. Mohanty. 2009. “The Unique Structure of A‐Tracts and Intrinsic DNA Bending.” Quarterly Reviews of Biophysics 42: 41–81.
Harwood, C. R., and S. M. Cutting. 1990. Molecular Biological Methods for Bacillus. Wiley. http://www.worldcat.org/title/molecular‐biological‐methods‐for‐bacillus/oclc/21482555.
Helmann, J. D. 1995. “Compilation and Analysis of Bacillus subtilis Sigma A‐Dependent Promoter Sequences: Evidence for Extended Contact Between RNA Polymerase and Upstream Promoter DNA.” Nucleic Acids Research 23: 2351–2360.
Hoch, J. A. 1993. “Regulation of the Phosphorelay and the Initiation of Sporulation in Bacillus subtilis.” Annual Review of Microbiology 47: 441–465.
Ivanova, N., A. Sorokin, I. Anderson, et al. 2003. “Genome Sequence of Bacillus cereus and Comparative Analysis With Bacillus anthracis.” Nature 423: 87–91.
Jiang, M., W. Shao, M. Perego, and J. A. Hoch. 2000. “Multiple Histidine Kinases Regulate Entry Into Stationary Phase and Sporulation in Bacillus subtilis.” Molecular Microbiology 38: 535–542.
Johnson, M., I. Zaretskaya, Y. Raytselis, Y. Merezhuk, S. McGinnis, and T. L. Madden. 2008. “NCBI BLAST: A Better Web Interface.” Nucleic Acids Research 36: W5–W9.
Kiehler, B., L. Haggett, and M. Fujita. 2017. “The PAS Domains of the Major Sporulation Kinase in Bacillus subtilis Play a Role in Tetramer Formation That Is Essential for the Autokinase Activity.” Microbiology 6: 1–12.
Kim, J., S. Klooster, and D. J. Shapiro. 1995. “Intrinsically Bent DNA in a Eukaryotic Transcription Factor Recognition Sequence Potentiates Transcription Activation.” Journal of Biological Chemistry 270: 1282–1288.
Koo, B. M., G. Kritikos, J. D. Farelli, et al. 2017. “Construction and Analysis of Two Genome‐Scale Deletion Libraries for Bacillus subtilis.” Cell Systems 4: 291–305.e7.
Lapidus, A., E. Goltsman, S. Auger, et al. 2008. “Extending the Bacillus cereus Group Genomics to Putative Food‐Borne Pathogens of Different Toxicity.” Chemico‐Biological Interactions 171: 236–249.
Letunic, I., R. R. Copley, B. Pils, S. Pinkert, J. Schultz, and P. Bork. 2006. “SMART 5: Domains in the Context of Genomes and Networks.” Nucleic Acids Research 34: D257–D260.
Liu, W., Z. He, F. Gao, J. Yan, and X. Huang. 2018. “Sensor Kinase KinB and Its Pathway‐Associated Key Factors Sense the Signal of Nutrition Starvation in Sporulation of Bacillus subtilis.” Microbiology 7: e00566.
Madeira, F., N. Madhusoodanan, J. Lee, et al. 2024. “The EMBL‐EBI Job Dispatcher Sequence Analysis Tools Framework in 2024.” Nucleic Acids Research 52: W521–W525.
Marathe, A., B. Zarazúa‐Osorio, P. Srivastava, and M. Fujita. 2023. “The Master Regulator for Entry Into Sporulation in Bacillus subtilis Becomes a Mother Cell‐Specific Transcription Factor for Forespore Engulfment.” Molecular Microbiology 120: 439–461.
Mizuno, T. 1987. “Random Cloning of Bent DNA Segments From Escherichia coli Chromosome and Primary Characterization of Their Structures.” Nucleic Acids Research 15: 6827–6841.
Molle, V., M. Fujita, S. T. Jensen, et al. 2003. “The Spo0A Regulon of Bacillus subtilis.” Molecular Microbiology 50: 1683–1701.
Narula, J., M. Fujita, and O. A. Igoshin. 2016. “Functional Requirements of Cellular Differentiation: Lessons From Bacillus subtilis.” Current Opinion in Microbiology 34: 38–46.
Narula, J., A. Kuchina, F. Zhang, M. Fujita, G. M. Suel, and O. A. Igoshin. 2016. “Slowdown of Growth Controls Cellular Differentiation.” Molecular Systems Biology 12: 871.
Nicolas, P., L. Bize, F. Muri, et al. 2002. “Mining Bacillus subtilis Chromosome Heterogeneities Using Hidden Markov Models.” Nucleic Acids Research 30: 1418–1426.
Pogliano, J., M. D. Sharp, and K. Pogliano. 2002. “Partitioning of Chromosomal DNA During Establishment of Cellular Asymmetry in Bacillus subtilis.” Journal of Bacteriology 184: 1743–1749.
Predich, M., G. Nair, and I. Smith. 1992. “Bacillus subtilis Early Sporulation Genes kinA, spo0F, and spo0A Are Transcribed by the RNA Polymerase Containing Sigma H.” Journal of Bacteriology 174: 2771–2778.
Read, T. D., S. N. Peterson, N. Tourasse, et al. 2003. “The Genome Sequence of Bacillus anthracis Ames and Comparison to Closely Related Bacteria.” Nature 423: 81–86.
Roberts, M. S., L. K. Nakamura, and F. M. Cohan. 1996. “Bacillus vallismortis sp. nov., a Close Relative of Bacillus subtilis, Isolated From Soil in Death Valley, California.” International Journal of Systematic Bacteriology 46: 470–475.
Ryder, K., S. Silver, A. L. DeLucia, E. Fanning, and P. Tegtmeyer. 1986. “An Altered DNA Conformation in Origin Region I Is a Determinant for the Binding of SV40 Large T Antigen.” Cell 44: 719–725.
Sambrook, J., and D. Russell. 2001. Molecular Cloning: A Laboratory Manual. 3rd ed. Cold Spring Harbor Laboratory Press.
Sayers, E. W., M. Cavanaugh, L. Frisse, et al. 2025. “GenBank 2025 Update.” Nucleic Acids Research 53: D56–D61.
Schroeder, J. W., and L. A. Simmons. 2013. “Complete Genome Sequence of Bacillus subtilis Strain PY79.” Genome Announcements 1: e01085‐13.
Stephenson, K., and J. A. Hoch. 2002. “Evolution of Signalling in the Sporulation Phosphorelay.” Molecular Microbiology 46: 297–304.
Tojo, S., K. Hirooka, and Y. Fujita. 2013. “Expression of kinA and kinB of Bacillus subtilis, Necessary for Sporulation Initiation, Is Under Positive Stringent Transcription Control.” Journal of Bacteriology 195: 1656–1665.
Valenzuela Ruiz, V., G. Santoyo, L. J. Gomez Godinez, L. A. Cira Chavez, F. I. Parra Cota, and S. de Los Santos Villalobos. 2023. “Complete Genome Sequencing of Bacillus Cabrialesii TE3(T): A Plant Growth‐Promoting and Biological Control Agent Isolated From Wheat (Triticum turgidum subsp. durum) in the Yaqui Valley.” Current Research in Microbial Sciences 4: 100193.
Vellanoweth, R. L., and J. C. Rabinowitz. 1992. “The Influence of Ribosome‐Binding‐Site Elements on Translational Efficiency in Bacillus Subtilis and Escherichia coli In Vivo.” Molecular Microbiology 6: 1105–1114.
Wang, A., and G. J. Ash. 2015. “Whole Genome Phylogeny of Bacillus by Feature Frequency Profiles (FFP).” Scientific Reports 5: 13644.
Wang, S. T., B. Setlow, E. M. Conlon, et al. 2006. “The Forespore Line of Gene Expression in Bacillus subtilis.” Journal of Molecular Biology 358: 16–37.
Zahid, S. H., and M. Fujita. 2026. “Differential Signaling Roles of the KinA‐KinE Sensor Kinases in Regulating Spo0A, the Master Regulator of Bacillus subtilis Cell‐Fate Decisions.” Current Opinion in Microbiology 92: 102791.
Zarazúa‐Osorio, B., P. Srivastava, A. Marathe, S. H. Zahid, and M. Fujita. 2025. “Autoregulation of the Master Regulator Spo0A Controls Cell‐Fate Decisions in Bacillus subtilis.” Molecular Microbiology 123: 305–329.
Zhang, Z., L. Yin, X. Li, C. Zhang, C. Liu, and Z. Wu. 2018. “The Complete Genome Sequence of Bacillus Halotolerans ZB201702 Isolated From a Drought‐ and Salt‐Stressed Rhizosphere Soil.” Microbial Pathogenesis 123: 246–249.
Grant Information: E-2099-20220331 Welch Foundation
Contributed Indexing: Keywords: Bacillus subtilis; histidine kinase; phosphorelay; response regulator; sporulation
Local Abstract: [plain-language-summary] Spore‐forming bacteria survive starvation by entering sporulation, but how this developmental switch is controlled is not fully understood. We show that the master regulator Spo0A controls the major sporulation kinase gene kinA through three DNA‐binding sites and the shape of the DNA itself. Together, these features help regulate the transition from growth to sporulation.
Substance Nomenclature: 0 (Bacterial Proteins)
0 (Spo0A protein, Bacillus subtilis)
EC 2.7.- (Protein Kinases)
0 (Transcription Factors)
0 (kinA protein, Bacillus subtilis)
0 (DNA, Bacterial)
Entry Date(s): Date Created: 20260728 Date Completed: 20261007 Latest Revision: 20261007
Update Code: 20261008
DOI: 10.1111/mmi.70100
PMID: 42520298
Βάση Δεδομένων: MEDLINE
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  Data: The Master Regulator Spo0A Integrates DNA Sequence and Shape to Regulate the Sporulation Kinase Gene kinA in Bacillus subtilis.
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  Data: <searchLink fieldCode="AU" term="%22Zahid+SH%22">Zahid SH</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Zarazúa-Osorio+B%22">Zarazúa-Osorio B</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Escobedo+R%22">Escobedo R</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Ullah+S%22">Ullah S</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Dona+SKK%22">Dona SKK</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Fujita+M%22">Fujita M</searchLink>; Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
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  Data: <searchLink fieldCode="MM" term="%22Bacillus+subtilis%22">Bacillus subtilis*</searchLink>/<searchLink fieldCode="MM" term="%22Bacillus+subtilis+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacillus+subtilis%22">Bacillus subtilis*</searchLink>/<searchLink fieldCode="MM" term="%22Bacillus+subtilis+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Protein+Kinases%22">Protein Kinases*</searchLink>/<searchLink fieldCode="MM" term="%22Protein+Kinases+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Protein+Kinases%22">Protein Kinases*</searchLink>/<searchLink fieldCode="MM" term="%22Protein+Kinases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription+Factors%22">Transcription Factors*</searchLink>/<searchLink fieldCode="MM" term="%22Transcription+Factors+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription+Factors%22">Transcription Factors*</searchLink>/<searchLink fieldCode="MM" term="%22Transcription+Factors+genetics%22">genetics</searchLink><br /><searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Bacterial%22">Gene Expression Regulation, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Bacterial+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Spores%2C+Bacterial%22">Spores, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22Spores%2C+Bacterial+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Spores%2C+Bacterial%22">Spores, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22Spores%2C+Bacterial+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22DNA%2C+Bacterial%22">DNA, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22DNA%2C+Bacterial+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22DNA%2C+Bacterial%22">DNA, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22DNA%2C+Bacterial+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Promoter+Regions%2C+Genetic%22">Promoter Regions, Genetic</searchLink> ; <searchLink fieldCode="MH" term="%22Phosphorylation%22">Phosphorylation</searchLink> ; <searchLink fieldCode="MH" term="%22Transcription%2C+Genetic%22">Transcription, Genetic</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Sporulation in starved Bacillus subtilis depends on precise control of kinA, which encodes the major phosphorelay kinase that generates the threshold level of phosphorylated Spo0A (Spo0A~P) required for entry into sporulation. Here, we define the regulatory logic that shapes kinA expression and uncover structural features that influence Spo0A~P recruitment. First, we show that the kinA promoter integrates positive and negative Spo0A~P inputs through a composite three-site 0A-box architecture. Distinct affinities and cooperative interactions among the three sites generate a controlled output in which activating and repressive inputs are balanced during starvation, maintaining basal-to-moderate kinA transcription. Second, we identify intrinsic DNA bending as a sequence-independent mechanism that enhances Spo0A~P engagement, promoting low-specificity interactions that may contribute to transcriptional regulation and more broadly chromosome organization. Finally, we show that both the kinA promoter and KinA protein domains diverge between pathogenic and nonpathogenic Bacillus species, reflecting niche-specific evolutionary pressures on sporulation initiation. Together, these findings support an integrated model in which promoter architecture and DNA shape collectively tune Spo0A~P dependent regulation of kinA.<br /> (© 2026 John Wiley & Sons Ltd.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Ben‐Yehuda, S., D. Z. Rudner, and R. Losick. 2003. “RacA, a Bacterial Protein That Anchors Chromosomes to the Cell Poles.” Science 299: 532–536.<br />Bossi, L., and D. M. Smith. 1984. “Conformational Change in the DNA Associated With an Unusual Promoter Mutation in a tRNA Operon of Salmonella.” Cell 39: 643–652.<br />Burbulys, D., K. A. Trach, and J. A. Hoch. 1991. “Initiation of Sporulation in B. subtilis Is Controlled by a Multicomponent Phosphorelay.” Cell 64: 545–552.<br />Carniol, K., P. Eichenberger, and R. Losick. 2004. “A Threshold Mechanism Governing Activation of the Developmental Regulatory Protein Sigma F in Bacillus subtilis.” Journal of Biological Chemistry 279: 14860–14870.<br />Chastanet, A., and R. Losick. 2011. “Just‐In‐Time Control of Spo0A Synthesis in Bacillus subtilis by Multiple Regulatory Mechanisms.” Journal of Bacteriology 193: 6366–6374.<br />Chen, Z., P. Srivastava, B. Zarazua‐Osorio, A. Marathe, M. Fujita, and O. A. Igoshin. 2022. “Bacillus subtilis Histidine Kinase KinC Activates Biofilm Formation by Controlling Heterogeneity of Single‐Cell Responses.” MBio 13: e0169421.<br />Devi, S. N., B. Kiehler, L. Haggett, and M. Fujita. 2015. “Evidence That Autophosphorylation of the Major Sporulation Kinase in Bacillus subtilis Is Able to Occur in Trans.” Journal of Bacteriology 197: 2675–2684.<br />Devi, S. N., M. Vishnoi, B. Kiehler, L. Haggett, and M. Fujita. 2015. “In Vivo Functional Characterization of the Transmembrane Histidine Kinase KinC in Bacillus subtilis.” Microbiology 161: 1092–1104.<br />Dutta, R., L. Qin, and M. Inouye. 1999. “Histidine Kinases: Diversity of Domain Organization.” Molecular Microbiology 34: 633–640.<br />Ellermeier, C. D., E. C. Hobbs, J. E. Gonzalez‐Pastor, and R. Losick. 2006. “A Three‐Protein Signaling Pathway Governing Immunity to a Bacterial Cannibalism Toxin.” Cell 124: 549–559.<br />Elufisan, T. O., and N. M. Rosas‐Garcia. 2025. “Whole Genome Sequence Analysis of Pigmented Bacillus Inaquosorum LBA001 Revealed Biosynthetic Gene Clusters for a Variety of Secondary Metabolites.” Antonie Van Leeuwenhoek 118: 107.<br />Errington, J. 2003. “Regulation of Endospore Formation in Bacillus subtilis.” Nature Reviews. Microbiology 1: 117–126.<br />Eswaramoorthy, P., A. Dravis, S. N. Devi, M. Vishnoi, H. A. Dao, and M. Fujita. 2011. “Expression Level of a Chimeric Kinase Governs Entry Into Sporulation in Bacillus subtilis.” Journal of Bacteriology 193: 6113–6122.<br />Eswaramoorthy, P., D. Duan, J. Dinh, A. Dravis, S. N. Devi, and M. Fujita. 2010. “The Threshold Level of the Sensor Histidine Kinase KinA Governs Entry Into Sporulation in Bacillus subtilis.” Journal of Bacteriology 192: 3870–3882.<br />Eswaramoorthy, P., and M. Fujita. 2010. “Systematic Domain Deletion Analysis of the Major Sporulation Kinase in Bacillus subtilis.” Journal of Bacteriology 192: 1744–1748.<br />Eswaramoorthy, P., T. Guo, and M. Fujita. 2009. “In Vivo Domain‐Based Functional Analysis of the Major Sporulation Sensor Kinase, KinA, in Bacillus subtilis.” Journal of Bacteriology 191: 5358–5368.<br />Fihn, C. A., and E. E. Carlson. 2021. “Targeting a Highly Conserved Domain in Bacterial Histidine Kinases to Generate Inhibitors With Broad Spectrum Activity.” Current Opinion in Microbiology 61: 107–114.<br />Fujita, M. 2000. “Temporal and Selective Association of Multiple Sigma Factors With RNA Polymerase During Sporulation in Bacillus subtilis.” Genes to Cells 5: 79–88.<br />Fujita, M., J. E. Gonzalez‐Pastor, and R. Losick. 2005. “High‐ and Low‐Threshold Genes in the Spo0A Regulon of Bacillus subtilis.” Journal of Bacteriology 187: 1357–1368.<br />Fujita, M., and R. Losick. 2003. “The Master Regulator for Entry Into Sporulation in Bacillus subtilis Becomes a Cell‐Specific Transcription Factor After Asymmetric Division.” Genes & Development 17: 1166–1174.<br />Fujita, M., and R. Losick. 2005. “Evidence That Entry Into Sporulation in Bacillus subtilis Is Governed by a Gradual Increase in the Level and Activity of the Master Regulator Spo0A.” Genes & Development 19: 2236–2244.<br />Fujita, M., and Y. Sadaie. 1998a. “Feedback Loops Involving Spo0A and AbrB in In Vitro Transcription of the Genes Involved in the Initiation of Sporulation in Bacillus subtilis.” Journal of Biochemistry 124: 98–104.<br />Fujita, M., and Y. Sadaie. 1998b. “Promoter Selectivity of the Bacillus subtilis RNA Polymerase sigmaA and sigmaH Holoenzymes.” Journal of Biochemistry 124: 89–97.<br />Grossman, A. D. 1995. “Genetic Networks Controlling the Initiation of Sporulation and the Development of Genetic Competence in Bacillus subtilis.” Annual Review of Genetics 29: 477–508.<br />Gupta, R. S., S. Patel, N. Saini, and S. Chen. 2020. “Robust Demarcation of 17 Distinct Bacillus Species Clades, Proposed as Novel Bacillaceae Genera, by Phylogenomics and Comparative Genomic Analyses: Description of Robertmurraya kyonggiensis sp. Nov. and Proposal for an Emended Genus Bacillus Limiting It Only to the Members of the Subtilis and Cereus Clades of Species.” International Journal of Systematic and Evolutionary Microbiology 70: 5753–5798.<br />Haggett, L., A. Bhasin, P. Srivastava, and M. Fujita. 2018. “A Revised Model for the Control of Fatty Acid Synthesis by Master Regulator Spo0A in Bacillus subtilis.” Molecular Microbiology 108: 424–442.<br />Haran, T. E., and U. Mohanty. 2009. “The Unique Structure of A‐Tracts and Intrinsic DNA Bending.” Quarterly Reviews of Biophysics 42: 41–81.<br />Harwood, C. R., and S. M. Cutting. 1990. Molecular Biological Methods for Bacillus. Wiley. http://www.worldcat.org/title/molecular‐biological‐methods‐for‐bacillus/oclc/21482555.<br />Helmann, J. D. 1995. “Compilation and Analysis of Bacillus subtilis Sigma A‐Dependent Promoter Sequences: Evidence for Extended Contact Between RNA Polymerase and Upstream Promoter DNA.” Nucleic Acids Research 23: 2351–2360.<br />Hoch, J. A. 1993. “Regulation of the Phosphorelay and the Initiation of Sporulation in Bacillus subtilis.” Annual Review of Microbiology 47: 441–465.<br />Ivanova, N., A. Sorokin, I. Anderson, et al. 2003. “Genome Sequence of Bacillus cereus and Comparative Analysis With Bacillus anthracis.” Nature 423: 87–91.<br />Jiang, M., W. Shao, M. Perego, and J. A. Hoch. 2000. “Multiple Histidine Kinases Regulate Entry Into Stationary Phase and Sporulation in Bacillus subtilis.” Molecular Microbiology 38: 535–542.<br />Johnson, M., I. Zaretskaya, Y. Raytselis, Y. Merezhuk, S. McGinnis, and T. L. Madden. 2008. “NCBI BLAST: A Better Web Interface.” Nucleic Acids Research 36: W5–W9.<br />Kiehler, B., L. Haggett, and M. Fujita. 2017. “The PAS Domains of the Major Sporulation Kinase in Bacillus subtilis Play a Role in Tetramer Formation That Is Essential for the Autokinase Activity.” Microbiology 6: 1–12.<br />Kim, J., S. Klooster, and D. J. Shapiro. 1995. “Intrinsically Bent DNA in a Eukaryotic Transcription Factor Recognition Sequence Potentiates Transcription Activation.” Journal of Biological Chemistry 270: 1282–1288.<br />Koo, B. M., G. Kritikos, J. D. Farelli, et al. 2017. “Construction and Analysis of Two Genome‐Scale Deletion Libraries for Bacillus subtilis.” Cell Systems 4: 291–305.e7.<br />Lapidus, A., E. Goltsman, S. Auger, et al. 2008. “Extending the Bacillus cereus Group Genomics to Putative Food‐Borne Pathogens of Different Toxicity.” Chemico‐Biological Interactions 171: 236–249.<br />Letunic, I., R. R. Copley, B. Pils, S. Pinkert, J. Schultz, and P. Bork. 2006. “SMART 5: Domains in the Context of Genomes and Networks.” Nucleic Acids Research 34: D257–D260.<br />Liu, W., Z. He, F. Gao, J. Yan, and X. Huang. 2018. “Sensor Kinase KinB and Its Pathway‐Associated Key Factors Sense the Signal of Nutrition Starvation in Sporulation of Bacillus subtilis.” Microbiology 7: e00566.<br />Madeira, F., N. Madhusoodanan, J. Lee, et al. 2024. “The EMBL‐EBI Job Dispatcher Sequence Analysis Tools Framework in 2024.” Nucleic Acids Research 52: W521–W525.<br />Marathe, A., B. Zarazúa‐Osorio, P. Srivastava, and M. Fujita. 2023. “The Master Regulator for Entry Into Sporulation in Bacillus subtilis Becomes a Mother Cell‐Specific Transcription Factor for Forespore Engulfment.” Molecular Microbiology 120: 439–461.<br />Mizuno, T. 1987. “Random Cloning of Bent DNA Segments From Escherichia coli Chromosome and Primary Characterization of Their Structures.” Nucleic Acids Research 15: 6827–6841.<br />Molle, V., M. Fujita, S. T. Jensen, et al. 2003. “The Spo0A Regulon of Bacillus subtilis.” Molecular Microbiology 50: 1683–1701.<br />Narula, J., M. Fujita, and O. A. Igoshin. 2016. “Functional Requirements of Cellular Differentiation: Lessons From Bacillus subtilis.” Current Opinion in Microbiology 34: 38–46.<br />Narula, J., A. Kuchina, F. Zhang, M. Fujita, G. M. Suel, and O. A. Igoshin. 2016. “Slowdown of Growth Controls Cellular Differentiation.” Molecular Systems Biology 12: 871.<br />Nicolas, P., L. Bize, F. Muri, et al. 2002. “Mining Bacillus subtilis Chromosome Heterogeneities Using Hidden Markov Models.” Nucleic Acids Research 30: 1418–1426.<br />Pogliano, J., M. D. Sharp, and K. Pogliano. 2002. “Partitioning of Chromosomal DNA During Establishment of Cellular Asymmetry in Bacillus subtilis.” Journal of Bacteriology 184: 1743–1749.<br />Predich, M., G. Nair, and I. Smith. 1992. “Bacillus subtilis Early Sporulation Genes kinA, spo0F, and spo0A Are Transcribed by the RNA Polymerase Containing Sigma H.” Journal of Bacteriology 174: 2771–2778.<br />Read, T. D., S. N. Peterson, N. Tourasse, et al. 2003. “The Genome Sequence of Bacillus anthracis Ames and Comparison to Closely Related Bacteria.” Nature 423: 81–86.<br />Roberts, M. S., L. K. Nakamura, and F. M. Cohan. 1996. “Bacillus vallismortis sp. nov., a Close Relative of Bacillus subtilis, Isolated From Soil in Death Valley, California.” International Journal of Systematic Bacteriology 46: 470–475.<br />Ryder, K., S. Silver, A. L. DeLucia, E. Fanning, and P. Tegtmeyer. 1986. “An Altered DNA Conformation in Origin Region I Is a Determinant for the Binding of SV40 Large T Antigen.” Cell 44: 719–725.<br />Sambrook, J., and D. Russell. 2001. Molecular Cloning: A Laboratory Manual. 3rd ed. Cold Spring Harbor Laboratory Press.<br />Sayers, E. W., M. Cavanaugh, L. Frisse, et al. 2025. “GenBank 2025 Update.” Nucleic Acids Research 53: D56–D61.<br />Schroeder, J. W., and L. A. Simmons. 2013. “Complete Genome Sequence of Bacillus subtilis Strain PY79.” Genome Announcements 1: e01085‐13.<br />Stephenson, K., and J. A. Hoch. 2002. “Evolution of Signalling in the Sporulation Phosphorelay.” Molecular Microbiology 46: 297–304.<br />Tojo, S., K. Hirooka, and Y. Fujita. 2013. “Expression of kinA and kinB of Bacillus subtilis, Necessary for Sporulation Initiation, Is Under Positive Stringent Transcription Control.” Journal of Bacteriology 195: 1656–1665.<br />Valenzuela Ruiz, V., G. Santoyo, L. J. Gomez Godinez, L. A. Cira Chavez, F. I. Parra Cota, and S. de Los Santos Villalobos. 2023. “Complete Genome Sequencing of Bacillus Cabrialesii TE3(T): A Plant Growth‐Promoting and Biological Control Agent Isolated From Wheat (Triticum turgidum subsp. durum) in the Yaqui Valley.” Current Research in Microbial Sciences 4: 100193.<br />Vellanoweth, R. L., and J. C. Rabinowitz. 1992. “The Influence of Ribosome‐Binding‐Site Elements on Translational Efficiency in Bacillus Subtilis and Escherichia coli In Vivo.” Molecular Microbiology 6: 1105–1114.<br />Wang, A., and G. J. Ash. 2015. “Whole Genome Phylogeny of Bacillus by Feature Frequency Profiles (FFP).” Scientific Reports 5: 13644.<br />Wang, S. T., B. Setlow, E. M. Conlon, et al. 2006. “The Forespore Line of Gene Expression in Bacillus subtilis.” Journal of Molecular Biology 358: 16–37.<br />Zahid, S. H., and M. Fujita. 2026. “Differential Signaling Roles of the KinA‐KinE Sensor Kinases in Regulating Spo0A, the Master Regulator of Bacillus subtilis Cell‐Fate Decisions.” Current Opinion in Microbiology 92: 102791.<br />Zarazúa‐Osorio, B., P. Srivastava, A. Marathe, S. H. Zahid, and M. Fujita. 2025. “Autoregulation of the Master Regulator Spo0A Controls Cell‐Fate Decisions in Bacillus subtilis.” Molecular Microbiology 123: 305–329.<br />Zhang, Z., L. Yin, X. Li, C. Zhang, C. Liu, and Z. Wu. 2018. “The Complete Genome Sequence of Bacillus Halotolerans ZB201702 Isolated From a Drought‐ and Salt‐Stressed Rhizosphere Soil.” Microbial Pathogenesis 123: 246–249.
– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: E-2099-20220331 Welch Foundation
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Bacillus subtilis; histidine kinase; phosphorelay; response regulator; sporulation<br /><i>Local Abstract: </i>[plain-language-summary] Spore‐forming bacteria survive starvation by entering sporulation, but how this developmental switch is controlled is not fully understood. We show that the master regulator Spo0A controls the major sporulation kinase gene kinA through three DNA‐binding sites and the shape of the DNA itself. Together, these features help regulate the transition from growth to sporulation.
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Bacterial Proteins)<br />0 (Spo0A protein, Bacillus subtilis)<br />EC 2.7.- (Protein Kinases)<br />0 (Transcription Factors)<br />0 (kinA protein, Bacillus subtilis)<br />0 (DNA, Bacterial)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260728 <i>Date Completed: </i>20261007 <i>Latest Revision: </i>20261007
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20261008
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1111/mmi.70100
– Name: AN
  Label: PMID
  Group: ID
  Data: 42520298
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42520298
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/mmi.70100
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 359
    Subjects:
      – SubjectFull: Gene Expression Regulation, Bacterial genetics
        Type: general
      – SubjectFull: Spores, Bacterial genetics
        Type: general
      – SubjectFull: Spores, Bacterial metabolism
        Type: general
      – SubjectFull: DNA, Bacterial genetics
        Type: general
      – SubjectFull: DNA, Bacterial metabolism
        Type: general
      – SubjectFull: Promoter Regions, Genetic
        Type: general
      – SubjectFull: Phosphorylation
        Type: general
      – SubjectFull: Transcription, Genetic
        Type: general
      – SubjectFull: Bacillus subtilis genetics
        Type: general
      – SubjectFull: Bacillus subtilis metabolism
        Type: general
      – SubjectFull: Bacterial Proteins genetics
        Type: general
      – SubjectFull: Bacterial Proteins metabolism
        Type: general
      – SubjectFull: Protein Kinases genetics
        Type: general
      – SubjectFull: Protein Kinases metabolism
        Type: general
      – SubjectFull: Transcription Factors metabolism
        Type: general
      – SubjectFull: Transcription Factors genetics
        Type: general
    Titles:
      – TitleFull: The Master Regulator Spo0A Integrates DNA Sequence and Shape to Regulate the Sporulation Kinase Gene kinA in Bacillus subtilis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
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            NameFull: Zahid SH
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            NameFull: Zarazúa-Osorio B
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            NameFull: Escobedo R
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            NameFull: Ullah S
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            NameFull: Dona SKK
      – PersonEntity:
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            NameFull: Fujita M
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          Dates:
            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1365-2958
          Numbering:
            – Type: volume
              Value: 126
            – Type: issue
              Value: 4
          Titles:
            – TitleFull: Molecular microbiology
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