A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.
A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.
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DOI：
10.1016/j.molcel.2009.12.001
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发表时间：
2009-12-25
期刊：
影响因子：
16
通讯作者：
Vakoc CR
中科院分区：
文献类型：
--
作者：
Blobel GA;Kadauke S;Wang E;Lau AW;Zuber J;Chou MM;Vakoc CR
混合谱系白血病（MLL）及其后生动物直系同源物与转录活性的表观遗传维持有关。为了确定MLL可能使分裂细胞中的活性转录永久化的机制，我们研究了其在细胞周期M期的作用。与其他组蛋白甲基转移酶检查，MLL仍然全球嵌入在凝聚的有丝分裂染色体。全基因组位置分析揭示了与间期相比，有丝分裂中MLL占据的重排模式，其特征是MLL强烈偏好占据有丝分裂中具有最高间期转录水平的基因。敲除实验表明，MLL是有丝分裂后快速激活其有丝分裂靶基因所必需的，这表明了书签功能。MLL在有丝分裂期间将Menin，RbBP 5和ASH2L与基因连接，但保留H3K4甲基化。这些发现暗示有丝分裂保留作为一个新的组成部分，MLL为基础的基因调控，这可能有助于在细胞分裂过程中的活性基因表达状态的遗传。
Mixed Lineage Leukemia (MLL) and its metazoan orthologs have been linked with the epigenetic maintenance of transcriptional activity. To identify mechanisms by which MLL might perpetuate active transcription in dividing cells, we investigated its role during M-phase of the cell cycle. Unlike other histone methyltransferases examined, MLL remained globally embedded within condensed mitotic chromosomes. Genome-wide location analysis revealed a rearranged pattern of MLL occupancy in mitosis compared with interphase, characterized by a strong preference for MLL to occupy genes in mitosis possessing the highest levels of interphase transcription. Knockdown experiments revealed that MLL is required for rapid post-mitotic reactivation of its mitotic target genes, suggesting a bookmarking function. MLL tethers Menin, RbBP5, and ASH2L to genes during mitosis, but is dispensable for preserving H3K4 methylation. These findings implicate mitotic retention as a novel component of MLL-based gene regulation which may facilitate inheritance of active gene expression states during cell division.
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