RING1A and BMI1 bookmark active genes via ubiquitination of chromatin-associated proteins.
RING1A and BMI1 bookmark active genes via ubiquitination of chromatin-associated proteins.
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DOI：
10.1093/nar/gkv1223
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发表时间：
2016-03-18
影响因子：
14.9
通讯作者：
Parvin JD
中科院分区：
文献类型：
--
作者：
Arora M;Packard CZ;Banerjee T;Parvin JD
在有丝分裂期间，随着转录过程的停止以及几乎所有转录相关机制从基因和启动子中撤离，染色质经历了巨大的结构变化。有丝分裂期间基因的分子书签是通过细胞分裂忠实传递细胞特异性转录模式的机制。我们之前发现活性启动子处的染色质泛素化是潜在的有丝分裂书签。在这项研究中，我们鉴定了参与有丝分裂前泛素沉积的酶。我们发现多梳复合体蛋白BMI1和RING1A调节与启动子结合的染色质相关蛋白的泛素化，一旦细胞进入G1期，这种修饰对于标记基因的表达是必要的。 RING1A 的耗尽，以及由此导致的泛素化使有丝分裂标记失活，对于 G1 期的进展、细胞存活和增殖是有害的。虽然多梳复合蛋白被认为主要通过转录抑制来调节基因表达，但在这项研究中，我们发现这两种多梳蛋白在有丝分裂到 G1 过渡期间调节活性基因的转录。
During mitosis the chromatin undergoes dramatic architectural changes with the halting of the transcriptional processes and evacuation of nearly all transcription associated machinery from genes and promoters. Molecular bookmarking of genes during mitosis is a mechanism of faithfully transmitting cell-specific transcription patterns through cell division. We previously discovered chromatin ubiquitination at active promoters as a potential mitotic bookmark. In this study, we identify the enzymes involved in the deposition of ubiquitin before mitosis. We find that the polycomb complex proteins BMI1 and RING1A regulate the ubiquitination of chromatin associated proteins bound to promoters, and this modification is necessary for the expression of marked genes once the cells enter G1. Depletion of RING1A, and thus inactivation of mitotic bookmarking by ubiquitination, is deleterious to progression through G1, cell survival and proliferation. Though the polycomb complex proteins are thought to primarily regulate gene expression by transcriptional repression, in this study, we discover that these two polycomb proteins regulate the transcription of active genes during the mitosis to G1 transition.