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Smek promotes corticogenesis through regulating Mbd3's stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis.

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العنوان: Smek promotes corticogenesis through regulating Mbd3's stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis.
المؤلفون: Byoung-San Moon, Hyung-Mun Yun, Wen-Hsuan Chang, Bradford H Steele, Mingyang Cai, Si Ho Choi, Wange Lu
المصدر: PLoS Biology, Vol 15, Iss 5, p e2001220 (2017)
بيانات النشر: Public Library of Science (PLoS), 2017.
سنة النشر: 2017
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: The fate of neural progenitor cells (NPCs) during corticogenesis is determined by a complex interplay of genetic or epigenetic components, but the underlying mechanism is incompletely understood. Here, we demonstrate that Suppressor of Mek null (Smek) interact with methyl-CpG-binding domain 3 (Mbd3) and the complex plays a critical role in self-renewal and neuronal differentiation of NPCs. We found that Smek promotes Mbd3 polyubiquitylation and degradation, blocking recruitment of the repressive Mbd3/nucleosome remodeling and deacetylase (NuRD) complex at the neurogenesis-associated gene loci, and, as a consequence, increasing acetyl histone H3 activity and cortical neurogenesis. Furthermore, overexpression of Mbd3 significantly blocked neuronal differentiation of NPCs, and Mbd3 depletion rescued neurogenesis defects seen in Smek1/2 knockout mice. These results reveal a novel molecular mechanism underlying Smek/Mbd3/NuRD axis-mediated control of NPCs' self-renewal and neuronal differentiation during mammalian corticogenesis.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1544-9173
1545-7885
Relation: http://europepmc.org/articles/PMC5414985?pdf=render; https://doaj.org/toc/1544-9173; https://doaj.org/toc/1545-7885
DOI: 10.1371/journal.pbio.2001220
URL الوصول: https://doaj.org/article/da9531bcfcc8425f90386b833305dca5
رقم الأكسشن: edsdoj.9531bcfcc8425f90386b833305dca5
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15449173
15457885
DOI:10.1371/journal.pbio.2001220