Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Mol Cell. 2009 Dec 25;36(6):970-83. doi: 10.1016/j.molcel.2009.12.001.
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.
混合谱系白血病（MLL）及其后生动物同源物 Trithorax 与转录活性的表观遗传维持有关。为了确定 MLL 在有丝分裂细胞中持续保持转录活性的机制，我们研究了其在细胞周期 M 期的作用。与其他研究的染色质修饰酶不同，我们发现 MLL 与包装在浓缩有丝分裂染色体中的基因启动子结合。全基因组定位分析鉴定了有丝分裂过程中 MLL 占据的一种全局重排模式，有利于在间期高度转录的基因。敲低实验表明，有丝分裂期间 MLL 在基因启动子上的保留可加速有丝分裂后转录的重新激活。MLL 在有丝分裂期间将 Menin、RbBP5 和 ASH2L 固定在其占据的位点，但对于保持组蛋白 H3K4 甲基化是可有可无的。这些发现表明有丝分裂书签是基于 Trithorax 的基因调控的一个组成部分，它可能有助于在细胞分裂过程中保持活跃的基因表达状态的遗传。
