Control of developmental regulator's by polycomb in human embryonic stem cells

被引:1828
作者
Lee, TI
Jenner, RG
Boyer, LA
Guenther, MG
Levine, SS
Kumar, RM
Chevalier, B
Johnstone, SE
Cole, MF
Isono, K
Koseki, H
Fuchikami, T
Abe, K
Murray, HL
Zucker, JP
Yuan, BB
Bell, GW
Herbolsheimer, E
Hannett, NM
Sun, KM
Odom, DT
Otte, AP
Volkert, TL
Bartel, DP
Melton, DA
Gifford, DK
Jaenisch, R
Young, RA
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] RIKEN, Ctr Allergy & Immunol, Dev Genet Grp, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
[4] RIKEN, Tsukuba Inst, BioResource Ctr, Technol & Dev Team Mammalian Cellular Dynam, Tsukuba, Ibaraki 2300045, Japan
[5] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands
[6] Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[7] MIT, CSAIL, Cambridge, MA 02139 USA
关键词
D O I
10.1016/j.cell.2006.02.043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. These genes are occupied by nucleosomes trimethylated at histone H3K27, are transcriptionally repressed, and contain some of the most highly conserved noncoding elements in the genome. We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes. These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation.
引用
收藏
页码:301 / 313
页数:13
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