在ES细胞酸盐规范中Dpy-30的作用通过对双价域内H3K4甲基化调节ES细胞酸盐规范中的作用
Hao Jiang1, Abhijit Shukla, Xiaoling Wang
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, 10065, USA.
Cell
|February 22, 2011
概括
哺乳动物Dpy-30蛋白调节胚胎干细胞 (ESCs) 中的素H3K4三甲基化 (H3K4me3). Dpy-30的枯竭会损害ESC分化,特别是神经谱系的发展,突出其在发育基因调节中的作用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 染色体生物学 染色体生物学
- 发育生物学 发展生物学
背景情况:
- 基因组H3K4甲基化 (H3K4me) 标记了活跃的基因.
- 双对应色素标记 (H3K4me和H3K27me) 是胚胎干细胞 (ESC) 中平衡发育基因的特征.
- 在ESC维护和分化中H3K4甲基化的确切功能尚不清楚.
研究的目的:
- 研究哺乳动物Dpy-30的作用,它是SET1/MLL基因组甲基转移酶复合物的子单元,在H3K4甲基化中的作用.
- 确定DPY-30和H3K4甲基化在ESC自我更新和分化中的功能意义.
主要方法:
- 在实验室中通过Dpy-30.0对H3K4甲基化的调制.
- 在Dpy-30耗尽时对染色体H3K4三甲基化 (H3K4me3) 的全基因组分析.
- 评估ESC自我更新和差异化潜力,特别是在神经系方面.
主要成果:
- Dpy-30在体外调节H3K4甲基化,并在整个基因组中调节H3K4me3.
- Dpy-30的耗尽不会影响ESC的自我更新,但会显著损害分化,尤其是神经分化.
- 基因诱导和H3K4me3在发育位置的缺陷伴随着分化障碍.
结论:
- Dpy-30对于调节H3K4me3至关重要,这是双价色色素标记的关键组成部分.
- 通过Dpy-30进行SET1/MLL复杂介导的H3K4甲基化在ESC命运过渡期间在发育基因调节中发挥着关键作用.
- 这项研究确定了DPY-30在控制ESC差异化潜力的功能性作用.
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