Abstract:
:Trimethylation on H3K27 (H3K27me3) mediated by Polycomb repressive complex 2 (PRC2) has been linked to embryonic stem cell (ESC) identity and pluripotency. EZH2, the catalytic subunit of PRC2, has been reported as the sole histone methyltransferase that methylates H3K27 and mediates transcriptional silencing. Analysis of Ezh2(-/-) ESCs suggests existence of an additional enzyme(s) catalyzing H3K27 methylation. We have identified EZH1, a homolog of EZH2 that is physically present in a noncanonical PRC2 complex, as an H3K27 methyltransferase in vivo and in vitro. EZH1 colocalizes with the H3K27me3 mark on chromatin and preferentially preserves this mark on development-related genes in Ezh2(-/-) ESCs. Depletion of Ezh1 in cells lacking Ezh2 abolishes residual methylation on H3K27 and derepresses H3K27me3 target genes, demonstrating a role of EZH1 in safeguarding ESC identity. Ezh1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity.
journal_name
Mol Celljournal_title
Molecular cellauthors
Shen X,Liu Y,Hsu YJ,Fujiwara Y,Kim J,Mao X,Yuan GC,Orkin SHdoi
10.1016/j.molcel.2008.10.016subject
Has Abstractpub_date
2008-11-21 00:00:00pages
491-502issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00732-6journal_volume
32pub_type
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