Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
Histone H3K9 methyltransferases regulate cortical growth by coordinating heterochromatin formation and neural progenitor dynamics. |
| Συγγραφείς: |
Warren, Sophie1, Hemmerich, Chris2, Podicheti, Ram2, Baizabal, José-Manuel1 mbaizaba@iu.edu |
| Πηγή: |
Development (0950-1991). Sep2026, Vol. 153 Issue 18, p1-19. 19p. |
| Θεματικοί όροι: |
*Histone methyltransferases, *Cerebral cortex development, *Microcephaly, *Neural stem cells, *Epigenetics, *Histones, *Mobile genetic elements, *Heterochromatin |
| Περίληψη: |
Packaging of DNA into heterochromatin is a fundamental mechanism of transcriptional silencing, yet its role in regulating neural progenitor behavior during brain development remains poorly understood. Trimethylation of histone H3 lysine 9 (H3K9me3), catalyzed by the methyltransferases SETDB1, SUV39H1 and SUV39H2, is a defining feature of heterochromatin, but functional redundancy among these enzymes has obscured their developmental roles. Here, we generated a cortex-specific triple knockout mouse model lacking Setdb1, Suv39h1 and Suv39h2 to directly interrogate H3K9me3 function during corticogenesis. Combined loss of H3K9 methyltransferases caused genome-wide depletion of H3K9me3, disruption of neural progenitor cell-cycle progression, and impaired cortical neurogenesis, resulting in microcephaly. H3K9 methyltransferases preserve neural progenitor identity and function by silencing clustered protocadherins, meiosisassociated genes and a cell-cycle restraint program through H3K9me3 deposition. Loss of H3K9me3 promoted local chromatin opening and increased transcription factor occupancy, enabling transposable elements to acquire cryptic enhancer activity and modulate proximal gene expression. Together, these findings establish H3K9me3 heterochromatin as an active regulator of neural progenitor dynamics and lineage fidelity, revealing a central epigenetic mechanism that restricts aberrant transcriptional programs to ensure cortical growth. [ABSTRACT FROM AUTHOR] |
| Βάση Δεδομένων: |
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