Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network
Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network
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DOI：
10.1038/ncb3418
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发表时间：
2016-11-01
影响因子：
21.3
通讯作者：
Navarro, Pablo
中科院分区：
文献类型：
--
作者：
Festuccia, Nicola;Dubois, Agnes;Navarro, Pablo
多能小鼠胚胎干细胞在几乎无限的细胞分裂过程中保持其身份。这种现象被称为自我更新，依赖于序列特异性转录因子（TF）的网络，需要子细胞准确地复制母体的基因表达模式。然而，在有丝分裂中发生了显著的染色体变化，通常导致TF从染色质中被驱逐。在这里，我们报告说，Esrrb，一个主要的多能性TF，在有丝分裂过程中仍然结合到关键的调控区域。我们表明，有丝分裂Esrrb结合是高度动态的，由其DNA结合基序的特异性识别驱动，并且与有丝分裂完成后靶基因的早期转录激活相关。这些结果表明，Esrrb可能作为一个有丝分裂书签因子，打开另一个角度来分子上理解的作用，序列特异性TF的自我更新，多能性和基因组重编程的表观遗传控制。
Pluripotent mouse embryonic stem cells maintain their identity throughout virtually infinite cell divisions. This phenomenon, referred to as self-renewal, depends on a network of sequence-specific transcription factors (TFs) and requires daughter cells to accurately reproduce the gene expression pattern of the mother. However, dramatic chromosomal changes take place in mitosis, generally leading to the eviction of TFs from chromatin. Here, we report that Esrrb, a major pluripotency TF, remains bound to key regulatory regions during mitosis. We show that mitotic Esrrb binding is highly dynamic, driven by specific recognition of its DNA-binding motif and is associated with early transcriptional activation of target genes after completion of mitosis. These results indicate that Esrrb may act as a mitotic bookmarking factor, opening another perspective to molecularly understand the role of sequence-specific TFs in the epigenetic control of self-renewal, pluripotency and genome reprogramming.