Language
English
Publication Date
8-1-2023
Journal
Nature Cell Biology
DOI
10.1038/s41556-023-01191-z
PMID
37460697
PMCID
PMC10896483
PubMedCentral® Posted Date
2-26-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
The epigenetic mechanisms that maintain differentiated cell states remain incompletely understood. Here we employed histone mutants to uncover a crucial role for H3K36 methylation in the maintenance of cell identities across diverse developmental contexts. Focusing on the experimental induction of pluripotency, we show that H3K36M-mediated depletion of H3K36 methylation endows fibroblasts with a plastic state poised to acquire pluripotency in nearly all cells. At a cellular level, H3K36M facilitates epithelial plasticity by rendering fibroblasts insensitive to TGFβ signals. At a molecular level, H3K36M enables the decommissioning of mesenchymal enhancers and the parallel activation of epithelial/stem cell enhancers. This enhancer rewiring is Tet dependent and redirects Sox2 from promiscuous somatic to pluripotency targets. Our findings reveal a previously unappreciated dual role for H3K36 methylation in the maintenance of cell identity by integrating a crucial developmental pathway into sustained expression of cell-type-specific programmes, and by opposing the expression of alternative lineage programmes through enhancer methylation.
Keywords
Methylation, Histones, Cell Differentiation, Epigenesis, Genetic, Fibroblasts, Cell Lineage
Published Open-Access
yes
Recommended Citation
Hoetker, Michael S; Yagi, Masaki; Di Stefano, Bruno; et al., "H3K36 Methylation Maintains Cell Identity by Regulating Opposing Lineage Programmes" (2023). Faculty, Staff and Students Publications. 8561.
https://digitalcommons.library.tmc.edu/baylor_docs/8561