Hierarchical chromatin polyvalency governs robust gene regulation and organogenesis
Precise temporal control of gene expression is fundamental for embryonic development, yet the epigenetic and chromatin basis governing transcriptional timing remain poorly understood. The bivalency model, characterized by coexistence of H3K4me3 and H3K27me3, has been proposed to mark a poised state ready for activation. However, this model has been challenged by lacking of rapid gene activation…
Embryonic development hinges on precise control of gene expression, yet epigenetic and chromatin mechanisms governing this process remain elusive. The bivalency model, wherein H3K4me3 and H3K27me3 coexist, was presumed to mark a poised state awaiting activation. However, this model's lack of rapid response to H3K27me3 depletion suggested H3K27me3's role may be limited.
Through temporal epigenomic profiling of post-implantation mouse embryos and the protein degradation tag (dTAG) system, we uncovered H2Aub as the primary repressor, not H3K27me3. A hierarchical repression architecture emerged, with H2Aub silencing transcription, while H3K27me3 and H3K9me3 fortified the silenced state in post-implantation embryos.
Stripping away this H2Aub-centered hierarchy disrupted temporal control of polyvalent gene activation, resulting in grave organogenesis issues. Mechanistically, H2Aub's acute absence disrupted the retinoic acid-FGF signaling pathway, causing somitogenesis arrest. Our findings reveal chromatin polyvalency as a multi-layered, hierarchical repression mechanism crucial for temporal control of gene expression during embryogenesis.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
