Stanford University, Stanford, California 94305, USA.
Nat Rev Genet. 2013 May;14(5):347-59. doi: 10.1038/nrg3413. Epub 2013 Apr 9.
Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have uncovered mutations in many chromatin regulators. These human genetic studies, along with studies in model organisms, are providing insight into chromatin regulatory mechanisms in neural development and how alterations to these mechanisms can cause cognitive deficits, such as intellectual disability. We discuss several implicated chromatin regulators, including BAF (also known as SWI/SNF) and CHD8 chromatin remodellers, HDAC4 and the Polycomb component EZH2. Interestingly, mutations in EZH2 and certain BAF complex components have roles in both neurodevelopmental disorders and cancer, and overlapping point mutations are suggesting functionally important residues and domains. We speculate on the contribution of these similar mutations to disparate disorders.
最近在人类神经发育和精神疾病方面的全基因组测序研究揭示了许多染色质调控因子的突变。这些人类遗传学研究，以及模式生物的研究，为我们提供了关于神经发育过程中染色质调控机制的深入了解，以及这些机制的改变如何导致认知缺陷，如智力障碍。我们讨论了几个涉及的染色质调控因子，包括 BAF（也称为 SWI/SNF）和 CHD8 染色质重塑因子、HDAC4 和 Polycomb 成分 EZH2。有趣的是，EZH2 和某些 BAF 复合物成分的突变在神经发育障碍和癌症中都有作用，重叠的点突变提示了功能重要的残基和结构域。我们推测这些相似的突变对不同疾病的贡献。
