Cell出版社旗下的Trends in Cell Biology杂志2013年第4期发表了永利yl23411官网登录汪方炜教授的综述文章："Histone modifications and mitosis: countermarks,
landmarks, and bookmarks”。
landmarks, and bookmarks”。
真核细胞内的基因组DNA缠绕于组蛋白八聚体形成核小体，后者构成染色质的基本结构单位。在过去的十几年间，组蛋白的翻译后修饰对基因的表观遗传调控以及DNA损伤修复等方面的研究非常热门。然而，有丝分裂特异性的组蛋白修饰的生物学功能的研究相对滞后，方兴未艾。
该文回顾了近几年关于有丝分裂特异性的组蛋白修饰（包括磷酸化、甲基化、乙酰化和泛素化等）的研究进展。譬如，由蛋白激酶Haspin所介导的组蛋白H3三号位苏氨酸的磷酸化能被Survivin蛋白所直接识别，从而招募染色体乘客复合体（Chromosomal Passenger Complex）至染色体的特定结构区（centromere）执行调控染色体分离的重要功能（Wang F. et al., Science, 2010; Curr Biol., 2011; J Cell Biol., 2012）。该文提出了一个整合性的观点，即组蛋白修饰作为“countermark”、“landmark”和“bookmark”等标记在有丝分裂期排斥、招募和记忆细胞分裂和基因转录的重要调控因子在染色体上的定位。这些组蛋白标记有助于有丝分裂期基因转录的下调，促进染色体的精确分离，进而维护基因组的稳定性。文章期待这方面研究的更大突破，进而揭示有丝分裂调控的新机制。
汪方炜博士和美国哈佛大学医学院的Jonathan Higgins博士为文章的共同通讯作者。
Fangwei Wang1*, Jonathan M.G. Higgins 2*
1 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
2 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
(* Co-corresponding authors)
Trends in Cell Biology, Volume 23, Issue 4, April 2013, Pages 175–184
Summary
The roles of post-translational histone modifications in regulating transcription and DNA damage have been widely studied and discussed. Although mitotic histone marks, particularly phosphorylation, were discovered four decades ago, their roles in mitosis have been outlined only in the past few years. Here we aim to provide an integrated view of how histone modifications act as countermarks, landmarks, and bookmarks to displace, recruit, and remember the location of regulatory proteins during and shortly after mitosis. These capabilities allow histone marks to help downregulate interphase functions such as transcription during mitosis, to facilitate chromatin events required to accomplish chromosome segregation, and to contribute to the maintenance of epigenetic states through mitosis.
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2013年4月
