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染色体改造器ISWI的结构和调节

Lijuan Yan^1,2, Li Wang^1,2, Yuanyuan Tian^1,2

¹MOE Key Laboratory of Protein Science, Tsinghua University, Beijing, 100084, China.

|December 6, 2016

概括

该研究揭示了AutoN域如何通过与其核心结合来抑制ISWI (模仿开关) 染色体重塑活性. 激素H4结合释放这种抑制,解释ISWI激活及其在染色质调节中的作用.

科学领域:

分子生物学
染色体生物学
结构生物学

背景情况:

ISWI (模仿开关) 是一种关键的染色体重塑剂,对于复制和转录等DNA过程至关重要.
它的活性由抑制性AutoN和NegC域调节,受素H4尾和DNA长度的影响.
在此之前,AutoN和NegC抑制和ISWI调节的确切机制尚不清楚.

研究的目的:

通过其AutoN域来阐明ISWI抑制的结构基础.
了解 histone H4 结合如何激活ISWI.
调查NegC领域在ISWI监管中的作用.

主要方法:

使用X射线结晶学来确定来自Myceliophthora thermophila的ISWI结构.
分析了单独的ISWI和与H4组合的结构.
生物化学测试被隐含地用于理解功能调节.

主要成果:

该AutoN域包含两个抑制元素,它们与core2域结合,使ISWI保持不活跃状态.
基因组H4与核心2域的结合,重叠一个AutoN结合位点,解释了ISWI激活.
NegC 域以异质调节ISWI,以应对核细胞外DNA的长度.

结论:

该AutoN域作为ISWI的催化核心的直接抑制剂.
基因组H4结合是ISWI的一个关键激活剂,通过对core2域的竞争性结合进行介导.
ISWI的调节域 (AutoN,NegC) 和与DNA/基因组的相互作用对于精确的染色体格局控制至关重要.

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