Brd4 Marks Select Genes on Mitotic Chromatin and Directs Postmitotic Transcription
Brd4 Marks Select Genes on Mitotic Chromatin and Directs Postmitotic Transcription
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DOI：
10.1091/mbc.e09-05-0380
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发表时间：
2009-12-01
影响因子：
3.3
通讯作者：
Ozato, Keiko
中科院分区：
文献类型：
--
作者：
Dey, Anup;Nishiyama, Akira;Ozato, Keiko
在进入有丝分裂时，许多转录因子与染色质解离，导致整体转录关闭。在有丝分裂过程中，一些基因被标记，以确保其表达在下一代细胞中的遗传。然而，有丝分裂基因标记的性质一直是模糊的。Brd 4是一种双溴结构域蛋白，在有丝分裂期间定位于染色体，并参与保持有丝分裂记忆。在间期，Brd 4与P-TEFb相互作用并作为全局转录辅激活因子发挥作用。我们发现，在整个有丝分裂过程中，Brd 4仍然与许多M/G1基因的转录起始位点结合，这些基因被编程为在有丝分裂结束时或结束后立即表达。相反，Brd 4不结合在细胞周期后期表达的基因。Brd 4与M/G1基因的结合在有丝分裂末期增加，与这些基因中组蛋白H3和H4的乙酰化增加一致。Brd 4结合的增加伴随着P-TEFb的募集和从头M/G1基因转录，这些事件在Brd 4敲低细胞中受损。总之，Brd 4在有丝分裂期间标记M/G1基因的转录记忆，并且在退出有丝分裂时，该标记充当启动它们在子细胞中的快速转录的信号。
On entry into mitosis, many transcription factors dissociate from chromatin, resulting in global transcriptional shutdown. During mitosis, some genes are marked to ensure the inheritance of their expression in the next generation of cells. The nature of mitotic gene marking, however, has been obscure. Brd4 is a double bromodomain protein that localizes to chromosomes during mitosis and is implicated in holding mitotic memory. In interphase, Brd4 interacts with P-TEFb and functions as a global transcriptional coactivator. We found that throughout mitosis, Brd4 remained bound to the transcription start sites of many M/G1 genes that are programmed to be expressed at the end of, or immediately after mitosis. In contrast, Brd4 did not bind to genes that are expressed at later phases of cell cycle. Brd4 binding to M/G1 genes increased at telophase, the end phase of mitosis, coinciding with increased acetylation of histone H3 and H4 in these genes. Increased Brd4 binding was accompanied by the recruitment of P-TEFb and de novo M/G1 gene transcription, the events impaired in Brd4 knockdown cells. In sum, Brd4 marks M/G1 genes for transcriptional memory during mitosis, and upon exiting mitosis, this mark acts as a signal for initiating their prompt transcription in daughter cells.