Cell出版社旗下的Trends in Cell Biology杂志12月13日在线发表我院汪方炜课题组和哈佛大学医学院Jonathan Higgins博士合作撰写的题为“Histone modifications and mitosis: countermarks, landmarks, and bookmarks”的综述文章。
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转录的表观遗传调控已得到非常广泛的研究。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严重滞后。
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）。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。
浙江大学生命科学研究院是该文的第一单位，汪方炜博士和Jonathan Higgins博士为共同通讯作者。
Trends in Cell Biology (2012). DOI:10.1016/j.tcb.2012.11.005.
Authors: 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)
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.
Keywords
histone; phosphorylation; acetylation; methylation; mitosis; centromere
浙江大学生命科学研究院
2012年12月18日
