TRPM7 酶被切割,释放出一种染色素修饰激酶
Grigory Krapivinsky1, Luba Krapivinsky1, Yunona Manasian1
1Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Enders Building 1309, 320 Longwood Avenue, Boston, MA 02115, USA.
Cell
|May 27, 2014
概括
TRPM7离子通道的激酶域被分裂,移动到核中,并修改基因组,影响基因表达. 这个过程将TRPM7的离子运输与表观遗传变化联系在一起.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- TRPM7 (过时受体潜力美拉斯7) 是一种具有离子通道和激酶活动的双功能蛋白质.
- 它在早期胚胎发育和细胞平衡中起着至关重要的作用.
- 将TRPM7的通道和激酶功能与基因调节联系在一起的精确机制尚未完全理解.
研究的目的:
- 为了研究TRPM7激酶域的细胞内定位和功能.
- 阐明TRPM7在通过表观遗传修饰调节基因表达中的作用.
- 探索TRPM7-介导的离子恒温与染色质重塑之间的联系.
主要方法:
- 细胞分离和西式涂抹检测切割的TRPM7激酶片段 (M7CKs).
- 免疫光和亚细胞局部化研究以追踪M7CKs.
- 染色体免疫沉 (ChIP) 试验用于评估M7CK与染色体和基因素酸化的结合.
- 测量细胞内自由的度.
主要成果:
- TRPM7激酶域被蛋白质分解分离并以细胞类型特定的方式转移到细胞核.
- 核M7CK与染色体重塑复合体相互作用,包括Polycomb组蛋白.
- 在TRPM7-依赖基因的促进者处,M7CKs酸化基因组,特别是H3Ser10,与基因活性相关.
- TRPM7的活性调节细胞内自由水平,从而影响M7CK与指转录因子的结合.
结论:
- TRPM7在离子通道活性,细胞内平衡和表观遗传基因调节之间起着至关重要的作用.
- 分裂的TRPM7激酶域通过直接影响基因素修饰来调节基因表达.
- 这些发现揭示了一个新的机制,即单个蛋白质集成信号通路来控制染色质结构和基因输出.
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