EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.
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.
Shen
Xiaohua
X
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Liu
Yingchun
Y
Hsu
Yu-Jung
YJ
Fujiwara
Yuko
Y
Kim
Jonghwan
J
Mao
Xiaohong
X
Yuan
Guo-Cheng
GC
Orkin
Stuart H
SH
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005809:Genes, Regulator; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008954:Models, Biological; D063151:Polycomb Repressive Complex 2; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; D000071221:Enhancer of Zeste Homolog 2 Protein; C498408:Ezh1 protein, mouse; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D008239:Lysine