人类胚胎干细胞中组蛋白H3赖氨酸4和赖氨酸27甲基化的全基因组分析。

Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells.

作者信息

Pan Guangjin, Tian Shulan, Nie Jeff, Yang Chuhu, Ruotti Victor, Wei Hairong, Jonsdottir Gudrun A, Stewart Ron, Thomson James A

机构信息

Genome Center of Wisconsin, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706-1580, USA.

出版信息

Cell Stem Cell. 2007 Sep 13;1(3):299-312. doi: 10.1016/j.stem.2007.08.003.

DOI:10.1016/j.stem.2007.08.003

PMID:18371364

Abstract

We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These commodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Commodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.

摘要

我们在人类胚胎干细胞中对全基因组范围内的多梳蛋白相关的组蛋白H3赖氨酸27三甲基化（H3K27me3）和三胸蛋白相关的组蛋白H3赖氨酸4三甲基化（H3K4me3）进行了定位。绝大多数H3K27me3与被H3K4me3修饰的基因共定位。这些被修饰的基因表达水平较低，并且在发育功能方面富集。另一组重要的基因既缺乏这两种修饰，在胚胎干细胞中表达水平也较低，但在生理反应而非发育过程中的基因功能方面富集。被修饰的基因在分化过程中能够迅速改变表达水平，但其他修饰类别的大量基因也能如此。多能性相关基因SOX2、POU5F1和NANOG在分化过程中受到抑制时，从仅被H3K4me3修饰转变为两种修饰的共定位。我们的结果表明，H3K27me3修饰在早期分化过程中发生变化，既解除了现有的抑制结构域，又赋予了新的抑制结构域，并且与H3K4me3的共定位并不局限于多能细胞。