DNA sequence-dependent epigenetic inheritance of gene silencing and histone H3K9 methylation.

DNA sequence-dependent epigenetic inheritance of gene silencing and histone H3K9 methylation.
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DOI:
10.1126/science.aaj2114
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发表时间:
2017-04-07
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Moazed D
Moazed D
中科院分区:
其他
文献类型:
--
作者:
Wang X;Moazed D

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表观遗传机制在维持基因表达状态的细胞记忆中起着重要作用。在裂变酵母中,组蛋白H3赖氨酸9 (H3K9)在异染色质结构域甲基化(H3K9me)。当编码促进H3K9去甲基化酶的epe1+被删除时,这些结构域可以被表观遗传。原生表观遗传状态是如何在epe1+细胞中稳定维持的尚不清楚。在这里,我们开发了一个系统来检查DNA序列和基因组背景在顺式遗传的h3k9me依赖性沉默状态的繁殖中的作用。我们发现,在epe1+细胞中,除了序列无关的H3K9me传播机制外,沉默的表观遗传还需要序列依赖性激活转录因子(ATF) -腺苷3 ',5 ' -单磷酸(cAMP)反应元件结合蛋白(CREB)家族转录因子在其原生染色体环境中的结合位点。因此,特定的DNA序列有助于H3K9me的顺式遗传和沉默的表观遗传状态。
Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9) is methylated (H3K9me) at heterochromatic domains. These domains can be epigenetically inherited when epe1+, encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in epe1+ cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state. We show that in epe1+ cells, in addition to sequence-independent mechanisms that propagate H3K9me, epigenetic inheritance of silencing requires binding sites for sequence-dependent activating transcription factor (ATF)–adenosine 3′,5′-monophosphate (cAMP) response element–binding protein (CREB) family transcription factors within their native chromosomal context. Thus, specific DNA sequences contribute to cis inheritance of H3K9me and silent epigenetic states.
在单细胞水平上表观遗传调节的动力学。
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