Academic Journal
Augmenting and directing long-range CRISPR-mediated activation in human cells.
| Τίτλος: | Augmenting and directing long-range CRISPR-mediated activation in human cells. |
|---|---|
| Συγγραφείς: | Tak YE; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA.; Department of Pathology, Harvard Medical School, Boston, MA, USA., Horng JE; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA., Perry NT; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA., Schultz HT; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA., Iyer S; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA., Yao Q; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Department of Pathology, Harvard Medical School, Boston, MA, USA.; Cell Circuits and Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Zou LS; Cell Circuits and Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Aryee MJ; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Department of Pathology, Harvard Medical School, Boston, MA, USA.; Cell Circuits and Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Pinello L; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Department of Pathology, Harvard Medical School, Boston, MA, USA.; Cell Circuits and Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Joung JK; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA. jjoung@mgh.harvard.edu.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA. jjoung@mgh.harvard.edu.; Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA. jjoung@mgh.harvard.edu.; Department of Pathology, Harvard Medical School, Boston, MA, USA. jjoung@mgh.harvard.edu. |
| Πηγή: | Nature methods [Nat Methods] 2021 Sep; Vol. 18 (9), pp. 1075-1081. Date of Electronic Publication: 2021 Aug 05. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101215604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1548-7105 (Electronic) Linking ISSN: 15487091 NLM ISO Abbreviation: Nat Methods Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Nature Pub. Group, c2004- |
| Ιατρικοί όροι (MeSH): | Clustered Regularly Interspaced Short Palindromic Repeats* , Promoter Regions, Genetic*, Gene Targeting/*methods , Transcription Factors/*genetics, Apolipoprotein C-III/genetics ; Apolipoproteins A/genetics ; Interleukin-2 Receptor alpha Subunit/genetics ; MyoD Protein/genetics ; beta-Globins/genetics ; Alleles ; Cell Line ; Enhancer Elements, Genetic ; Humans ; Polymorphism, Single Nucleotide ; Transcriptional Activation |
| Περίληψη: | Epigenetic editing is an emerging technology that uses artificial transcription factors (aTFs) to regulate expression of a target gene. Although human genes can be robustly upregulated by targeting aTFs to promoters, the activation induced by directing aTFs to distal transcriptional enhancers is substantially less robust and consistent. Here we show that long-range activation using CRISPR-based aTFs in human cells can be made more efficient and reliable by concurrently targeting an aTF to the target gene promoter. We used this strategy to direct target gene choice for enhancers capable of regulating more than one promoter and to achieve allele-selective activation of human genes by targeting aTFs to single-nucleotide polymorphisms embedded in distally located sequences. Our results broaden the potential applications of the epigenetic editing toolbox for research and therapeutics. (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| Σχόλια: | Erratum in: Nat Methods. 2022 Jul;19(7):899. doi: 10.1038/s41592-022-01561-9.. (PMID: 35761069) |
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| Grant Information: | R35 HG010717 United States HG NHGRI NIH HHS; R01 CA259058 United States CA NCI NIH HHS; R35 GM118158 United States GM NIGMS NIH HHS; RM1 HG009490 United States HG NHGRI NIH HHS; R01 CA211707 United States CA NCI NIH HHS; R00 HG008399 United States HG NHGRI NIH HHS; R01 CA204954 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (APOC3 protein, human) 0 (Apolipoprotein C-III) 0 (Apolipoproteins A) 0 (IL2RA protein, human) 0 (Interleukin-2 Receptor alpha Subunit) 0 (MyoD Protein) 0 (MyoD1 myogenic differentiation protein) 0 (Transcription Factors) 0 (apolipoprotein A-IV) 0 (beta-Globins) |
| Entry Date(s): | Date Created: 20210806 Date Completed: 20211011 Latest Revision: 20260924 |
| Update Code: | 20260924 |
| PubMed Central ID: | PMC8446310 |
| DOI: | 10.1038/s41592-021-01224-1 |
| PMID: | 34354266 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1548-7105 |
|---|---|
| DOI: | 10.1038/s41592-021-01224-1 |