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Mi-2/NuRD 复合物:造血发育、分化和癌症的关键表观遗传调控因子。

The Mi-2/NuRD complex: a critical epigenetic regulator of hematopoietic development, differentiation and cancer.

机构信息

Integrated Department of Immunology, National Jewish Health, Denver, CO, USA.

出版信息

Epigenetics. 2009 Nov 16;4(8):532-6. doi: 10.4161/epi.4.8.10108.

Abstract

The Mi-2/NuRD chromatin remodeling complex links multiple transcriptional regulatory processes including histone deacetylation, histone demethylation, nucleosome mobilization and recruitment of other regulatory proteins. In some contexts, Mi-2/NuRD functions as a barrier to transcriptional activation by working in opposition to other chromatin remodelers such as SWI/SNF. Alternatively, the Mi-2beta ATPase subunit of Mi-2/NuRD can promote transcription. Together, these gatekeeper functions of Mi-2/NuRD influence cell fate decisions by modulating transcriptional activity. Recent studies have shown the importance of Mi-2/NuRD both in maintaining hematopoietic stem cell (HSC) pools and in normal lineage progression. Furthermore, components of Mi-2/NuRD complexes are modular co-repressors/co-activators comprising multiple protein subunits that have been linked directly to oncogenesis and have potential as therapeutic targets for cancer treatment. Mi-2/NuRD's essential functions in metazoan cell fates and activities underscore its importance as a focal point of epigenetic research.

摘要

Mi-2/NuRD 染色质重塑复合物连接多个转录调控过程,包括组蛋白去乙酰化、组蛋白去甲基化、核小体动员和其他调节蛋白的募集。在某些情况下,Mi-2/NuRD 通过与 SWI/SNF 等其他染色质重塑因子相互作用,起到阻止转录激活的作用。或者,Mi-2/NuRD 的 Mi-2beta ATPase 亚基可以促进转录。这些 Mi-2/NuRD 的“守门员”功能通过调节转录活性来影响细胞命运决定。最近的研究表明,Mi-2/NuRD 在维持造血干细胞 (HSC) 池和正常谱系进展方面都很重要。此外,Mi-2/NuRD 复合物的组成部分是模块化的共抑制因子/共激活因子,包含多个与肿瘤发生直接相关的蛋白亚基,并且有可能成为癌症治疗的治疗靶点。Mi-2/NuRD 在后生动物细胞命运和活动中的重要功能突出了其作为表观遗传研究焦点的重要性。

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