Chromatin regulatory mechanisms in pluripotency.
Chromatin regulatory mechanisms in pluripotency.
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DOI：
10.1146/annurev-cellbio-051809-102012
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发表时间：
2010
影响因子：
11.3
通讯作者：
Crabtree GR
中科院分区：
文献类型：
--
作者：
Lessard JA;Crabtree GR
所有类型的干细胞都具有一个稳定的、可遗传的状态，允许多种发育途径。在过去的五年中，我们在了解这些可遗传状态以及它们开始或终止的方式方面取得了显著进展。直接与DNA结合并发挥充分作用的转录因子是最容易研究的，也许正是由于这个原因，它们与多能性的关系最为密切。此外，具有特殊功能的atp依赖性染色质重塑酶和组蛋白修饰酶的大型复合物也被遗传学研究认为与启动和/或维持多能性或多能性有关。这些依赖atp的重塑复合体中有几个发挥着非冗余的作用，esBAF复合体促进了诱导多能干细胞的重编程。最近发现，几乎所有组蛋白修饰都可以快速逆转，并且通常是高度动态的，这就提出了关于组蛋白修饰如何在多能性的稳定状态中发挥作用的新问题。遗传学研究的另一个令人惊讶的发现是，染色质调控因子突变的全球效应可以通过单个靶基因在很大程度上逆转。这些基因研究有助于确定未来机制研究的舞台，这些研究可能有助于利用多能性来实现治疗目标。
Stem cells of all types are characterized by a stable, heritable state permissive of multiple developmental pathways. The past five years have seen remarkable advances in understanding these heritable states and the ways that they are initiated or terminated. Transcription factors that bind directly to DNA and have sufficiency roles have been most easy to investigate and, perhaps for this reason, are most solidly implicated in pluripotency. In addition, large complexes of ATP-dependent chromatin-remodeling and histone-modification enzymes that have specialized functions have also been implicated by genetic studies in initiating and/or maintaining pluripotency or multipotency. Several of these ATP-dependent remodeling complexes play non-redundant roles, and the esBAF complex facilitates reprogramming of induced pluripotent stem cells. The recent finding that virtually all histone modifications can be rapidly reversed and are often highly dynamic has raised new questions about how histone modifications come to play a role in the steady state of pluripotency. Another surprise from genetic studies has been the frequency with which the global effects of mutations in chromatin regulators can be largely reversed by a single target gene. These genetic studies help define the arena for future mechanistic studies that might be helpful to harness pluripotency for therapeutic goals.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
64.5
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64.8
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