BANP打开色素并激活CpG岛调节的基因
Ralph S Grand1, Lukas Burger1,2, Cathrin Gräwe3
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature
|July 8, 2021
概括
研究人员确定BTG3相关核蛋白 (BANP) 是CpG岛屿促进者的关键转录因子. BANP激活重要的基因,其结合由DNA甲基化调节,影响染色质结构.
科学领域:
- 基因组学
- 表观遗传学
- 分子生物学
背景情况:
- CpG岛 (CGI) 促进体是哺乳动物RNA聚合酶II转录的主要部位.
- 由于对转录因子及其功能结合部位的了解不充分,对CGI促进剂的调控尚不明朗.
- 孤儿基因,如CGCG元素,在活跃促进体附近发现,但它们的结合因子是未知的.
研究的目的:
- 确定结合CGCG元素的转录因子.
- 阐明这种转录因子在CGI促进体中调节基因表达的作用.
- 了解DNA甲基化如何影响转录因子结合和染色质结构.
主要方法:
- 结合单分子足迹与相互作用蛋白质学.
- 在体外和体内研究转录因子结合.
- 在转录因子结合时分析了染色质可访问性和核细胞分相.
主要成果:
- 确定了BTG3相关核蛋白 (BANP) 作为结合CGCG元素的转录因子.
- BANP是CGI促进者的强有力的激活剂,控制干细胞和神经元中的必需代谢基因.
- 通过DNA甲基化抑制了BANP结合,使其功能仅限于非甲基化CGI.
- BANP与非甲基化基因结合导致染色体开放和核细胞分相.
结论:
- BANP是由CGI促进体调节的基本基因的关键激活剂.
- CGI促进剂活性取决于可以打开色素的甲基化敏感转录因子,如BANP.
- 基因甲基化通过表观遗传控制了BANP结合,影响了正常细胞和癌细胞的基因调节.
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