获得的组织特异性促进体双效性是成体细胞中PRC2需求的基础
Unmesh Jadhav1, Kodandaramireddy Nalapareddy1, Madhurima Saxena1
1Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Cell
|May 24, 2016
概括
在成年动物中,Polycomb Repressive Complex 2 (PRC2) 抑制具有双甲基化标记的组织特异基因. 失去PRC2导致异常基因表达,解释了自我更新组织的缺陷.
科学领域:
- 表观遗传学
- 基因调控
- 染色体生物学
背景情况:
- 胚胎干细胞 (ESC) 使用双价促进体 (H3K4me2/3和H3K27me3) 进行发育可塑性.
- 聚合物抑制复合物2 (PRC2) 沉积H3K27me3,在分化过程中通常会消失.
- 在成年自我更新组织中PRC2的作用及其与双价促剂的联系尚不清楚.
研究的目的:
- 研究双价促进剂和PRC2在成年自我更新组织中的作用.
- 阐明PRC2缺乏成年细胞基因失调的机制.
主要方法:
- 成年小鼠肠道和ESC的表观基因组分析.
- 染色体免疫沉以评估组织蛋白修饰 (H3K4me2/3和H3K27me3).
- 在野生型和PRC2缺乏的成年组织中分析基因表达.
主要成果:
- 与ESC相比,成年组织表现出较少和明显的双价促进体.
- 尽管H3K4me2/3,但具有双价促销物的组织特异基因在成年组织中被抑制.
- 缺乏PRC2导致这些双价基因的抑制,与H3K4me2/3水平成正比.
结论:
- 在成年动物中,PRC2 特别抑制获得组织受限促进体双价性的基因.
- 这种机制为PRC2缺乏的成年组织中的分子缺陷提供了统一的解释.
- 这些发现揭示了成年哺乳动物基因调节的特异性.
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