多梳蛋白对人类胚胎干细胞中发育调节因子的调控
Control of developmental regulators by Polycomb in human embryonic stem cells.
作者信息
Lee Tong Ihn, Jenner Richard G, Boyer Laurie A, Guenther Matthew G, Levine Stuart S, Kumar Roshan M, Chevalier Brett, Johnstone Sarah E, Cole Megan F, Isono Kyo-ichi, Koseki Haruhiko, Fuchikami Takuya, Abe Kuniya, Murray Heather L, Zucker Jacob P, Yuan Bingbing, Bell George W, Herbolsheimer Elizabeth, Hannett Nancy M, Sun Kaiming, Odom Duncan T, Otte Arie P, Volkert Thomas L, Bartel David P, Melton Douglas A, Gifford David K, Jaenisch Rudolf, Young Richard A
机构信息
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
出版信息
Cell. 2006 Apr 21;125(2):301-13. doi: 10.1016/j.cell.2006.02.043.
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.
多梳蛋白家族对于后生动物的早期发育至关重要，但其对人类发育的作用尚未完全明确。我们已在人类胚胎干细胞基因组的整个非重复区域绘制了多梳抑制复合物2（PRC2）亚基SUZ12的图谱。我们发现，SUZ12分布在两百多个编码关键发育调控因子的基因的大部分区域。这些基因被组蛋白H3K27三甲基化的核小体占据，处于转录抑制状态，并且包含基因组中一些高度保守的非编码元件。我们发现PRC2靶基因在胚胎干细胞分化过程中优先被激活，并且胚胎干细胞调控因子OCT4、SOX2和NANOG共同占据这些基因的很大一部分。这些结果表明，PRC2在胚胎干细胞中占据一组特殊的发育基因，这些基因必须被抑制以维持多能性，并且在胚胎干细胞分化过程中随时准备被激活。
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