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Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
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表观遗传机制通过p300/CBP扩散通过p300/CBP扩散基因素乙化
Masaki Kikuchi1, Satoshi Morita1, Masatoshi Wakamori1
1Laboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045, Japan.
Nature communications
|July 17, 2023
概括
这种p300/CREB结合蛋白 (CBP) 酶会读取乙化基因组H4尾巴,并在其他基因组上写出新的乙化标记,破坏核细胞的稳定,以控制基因转录.
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.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 希斯乙化调节了基因转录.
- 基因素乙化直接读写机制尚未得到充分理解.
研究的目的:
- 阐明通过p300/CREB结合蛋白 (CBP) 进行的基因素乙化直接读写机制.
- 确定p300/CBP识别和乙化基因组素N端尾的结构基础.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与核细胞结合的p300/CBP的结构.
- 生物化学试验,以评估组 histone 乙化和核酶体稳定性.
主要成果:
- 低温EM结构显示,p300/CBP通过其原体识别了乙化组合素H4 N终端尾部 (H4NTac).
- p300/CBP与DNA小沟相互作用,将其催化中心定位为乙化其他基因素N端尾,主要是H2BNT.
- H2BNT乙化促进了H2A-H2B与核细胞的解离.
结论:
- 对于表观遗传,p300/CBP在H3-H4四聚体内复制了基因组乙化标记.
- 乙化从H3-H4四分体转移到H2B-H2A二分体,破坏核细胞的稳定,并激活基因转录.
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