Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation.

Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation.
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DOI:
10.1016/j.devcel.2013.01.028
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发表时间:
2013-04-15
期刊:
影响因子:
11.8
通讯作者:
Disteche, Christine M.
Disteche, Christine M.
中科院分区:
生物学1区
文献类型:
--
作者:
Deng, Xinxian;Berletch, Joel B.;Ma, Wenxiu;Nguyen, Di Kim;Hiatt, Joseph B.;Noble, William S.;Shendure, Jay;Disteche, Christine M.

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哺乳动物中X基因的上调增加了X连锁转录本的表达水平,以补偿常染色体双等位基因的表达。在这里,我们介绍了在转录和转录后水平上增强X表达的分子机制。活性的小鼠X连锁启动子富含RNA聚合酶II(PolII-S5p)的起始形式和特定的组蛋白标记,包括H4K16ac和组蛋白变异体H2AZ。H4K16乙酰转移酶MOF是已知的介导果蝇X上调的酶,在哺乳动物X中也很丰富。小鼠ES细胞中MOF或MSL1的缺失会导致PolII-S5p和一组X连锁基因表达的特异性降低。对RNA半衰期数据集的分析表明,哺乳动物X连锁转录本的稳定性增加。无论是祖先的X连锁基因,还是新获得的X连锁基因,都是由类似的机制上调的,但程度不同,这表明基因的亚组受到明显的调控,这取决于它们的进化历史。
X upregulation in mammals increases levels of expressed X-linked transcripts to compensate for autosomal bi-allelic expression. Here, we present molecular mechanisms that enhance X expression at transcriptional and posttranscriptional levels. Active mouse X-linked promoters are enriched in the initiation form of RNA polymerase II (PolII-S5p) and in specific histone marks including H4K16ac and histone variant H2AZ. The H4K16 acetyltransferase MOF, known to mediate the Drosophila X upregulation, is also enriched on the mammalian X. Depletion of MOF or MSL1 in mouse ES cells causes a specific decrease in PolII-S5p and in expression of a subset of X-linked genes. Analyses of RNA half-life datasets show increased stability of mammalian X-linked transcripts. Both ancestral X-linked genes, defined as those conserved on chicken autosomes, and newly acquired X-linked genes are upregulated by similar mechanisms but to a different extent, suggesting that subsets of genes are distinctly regulated dependent on their evolutionary history.
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