Distinct specificity and functions of PRC2 subcomplexes in human stem cells and cardiac differentiation.

ABSTRACT: The dynamic regulation of epigenetic states relies on complex macromolecular interactions. PRC2, the methyltransferase complex depositing H3K27me3, interacts with distinct accessory proteins to form the mutually exclusive subcomplexes PHF1-PRC2.1, MTF2-PRC2.1, PHF19-PRC2.1, and PRC2.2. The functions of these subcomplexes are thought to be largely redundant. Here, we show that PRC2 subcomplexes have distinct roles in epigenetic repression of lineage-specific genes and stem cell differentiation. Using human pluripotent stem cells, we engineered a comprehensive set of separation-of-function mutants to dissect the roles of individual protein-protein and DNA-protein interactions. Our results show that PRC2.1 and PRC2.2 deposit H3K27me3 locus-specifically, resulting in opposing outcomes in cardi

SUBMITTER: Much C 

PROVIDER: S-EPMC12352605 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature