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基因表达表观遗传调控中的核小体去稳定化

Nucleosome destabilization in the epigenetic regulation of gene expression.

作者信息

Henikoff Steven

机构信息

Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.

出版信息

Nat Rev Genet. 2008 Jan;9(1):15-26. doi: 10.1038/nrg2206.

Abstract

Assembly, mobilization and disassembly of nucleosomes can influence the regulation of gene expression and other processes that act on eukaryotic DNA. Distinct nucleosome-assembly pathways deposit dimeric subunits behind the replication fork or at sites of active processes that mobilize pre-existing nucleosomes. Replication-coupled nucleosome assembly appears to be the default process that maintains silent chromatin, counteracted by active processes that destabilize nucleosomes. Nucleosome stability is regulated by the combined effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent nucleosome remodellers, post-translational modifications and histone variants. Recent studies suggest that histone turnover helps to maintain continuous access to sequence-specific DNA-binding proteins that regulate epigenetic inheritance, providing a dynamic alternative to histone-marking models for the propagation of active chromatin.

摘要

核小体的组装、动员和解聚可影响基因表达的调控以及作用于真核生物DNA的其他过程。不同的核小体组装途径会在复制叉后方或动员预先存在的核小体的活跃过程位点沉积二聚体亚基。复制偶联的核小体组装似乎是维持沉默染色质的默认过程,而活跃过程会破坏核小体的稳定性,从而起到抵消作用。核小体稳定性受核小体定位序列、组蛋白伴侣、ATP依赖的核小体重塑因子、翻译后修饰和组蛋白变体的综合影响。最近的研究表明,组蛋白周转有助于维持对调控表观遗传遗传的序列特异性DNA结合蛋白的持续访问,为活性染色质的传播提供了一种动态的组蛋白标记模型替代方案。

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