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首页> 外文期刊>Molecular cell >A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.
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A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.

机译：有丝分裂染色质中MLL占据的重新配置模式促进有丝分裂退出后快速转录重新激活。

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摘要

Mixed lineage leukemia (MLL) and its metazoan Trithorax orthologs have been linked with the epigenetic maintenance of transcriptional activity. To identify mechanisms by which MLL perpetuates active transcription in dividing cells, we investigated its role during M phase of the cell cycle. Unlike other chromatin-modifying enzymes examined, we found that MLL associates with gene promoters packaged within condensed mitotic chromosomes. Genome-wide location analysis identified a globally rearranged pattern of MLL occupancy during mitosis in a manner favoring genes that were highly transcribed during interphase. Knockdown experiments revealed that MLL retention at gene promoters during mitosis accelerates transcription reactivation following mitotic exit. MLL tethers Menin, RbBP5, and ASH2L to its occupied sites during mitosis, but is dispensable for preserving histone H3K4 methylation. These findings implicate mitotic bookmarking as a component of Trithorax-based gene regulation, which may facilitate inheritance of active gene expression states during cell division.
机译：混合谱系白血病（MLL）及其后生Trithorax直系同源物与转录活性的表观遗传维持有关。为了确定MLL维持分裂细胞中主动转录的机制，我们研究了其在细胞周期M期的作用。与检查的其他染色质修饰酶不同，我们发现MLL与包装在浓缩有丝分裂染色体内的基因启动子相关。全基因组位置分析确定了有丝分裂期间MLL占用的全球重排模式，其有利于在相间期高度转录的基因。击倒实验表明，在有丝分裂期间，MLL在基因启动子上的保留会加速有丝分裂退出后的转录重新激活。 MLL在有丝分裂期间将Menin，RbBP5和ASH2L束缚到其占据位点，但是对于保留组蛋白H3K4甲基化是必不可少的。这些发现暗示有丝分裂书签作为基于Trithorax的基因调控的一个组成部分，可能有助于细胞分裂过程中活跃基因表达状态的继承。

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