myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis.

myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis.
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在胚胎肌发生过程中,BAF60变体掺入BAF60变体重塑络合物中的肌瘤依赖性切换。

DOI:
10.1242/dev.108787
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发表时间:
2014-09
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Münsterberg A
Münsterberg A
中科院分区:
其他
文献类型:
--
作者:
Goljanek-Whysall K;Mok GF;Fahad Alrefaei A;Kennerley N;Wheeler GN;Münsterberg A

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肌生成涉及祖细胞的稳定定型,随后进行肌源性分化,这是由肌源性调节因子、microRNA和BAF染色质重塑复合物协调的过程。BAF 60 a、BAF 60 b和BAF 60 c是BAF复合物的结构亚基,它们与核心ATP酶Brg 1结合以提供功能特异性。BAF 60 c是必不可少的肌生成;然而,调节BAF/Brg 1复合物亚基组成的机制,特别是不同BAF 60变体的掺入,尚不清楚。在这里,我们揭示了它们在胚胎肌发生过程中的动态表达,并揭示了肌肉特异性microRNA(myomiRs)miR-133和miR-1/206在体节分化过程中对BAF 60 a和BAF 60 b的协同负调控。鸡胚中的microRNA抑制导致BAF 60 a或BAF 60 b水平增加,BAF/Brg 1亚基组成的伴随转换和延迟的肌生成。表型通过持续的BAF 60 a或BAF 60 b表达来模拟,并通过BAF 60 a或BAF 60 b的吗啉代敲低来拯救。这表明,myomiRs有助于选择BAF 60 c纳入Brg 1复合物,通过特异性靶向替代变体BAF 60 a和BAF 60 b在胚胎肌发生,并揭示了组织特异性非编码RNA和染色质重塑因子之间的相互作用赋予稳健性中胚层谱系确定。
Myogenesis involves the stable commitment of progenitor cells followed by the execution of myogenic differentiation, processes that are coordinated by myogenic regulatory factors, microRNAs and BAF chromatin remodeling complexes. BAF60a, BAF60b and BAF60c are structural subunits of the BAF complex that bind to the core ATPase Brg1 to provide functional specificity. BAF60c is essential for myogenesis; however, the mechanisms regulating the subunit composition of BAF/Brg1 complexes, in particular the incorporation of different BAF60 variants, are not understood. Here we reveal their dynamic expression during embryo myogenesis and uncover the concerted negative regulation of BAF60a and BAF60b by the muscle-specific microRNAs (myomiRs) miR-133 and miR-1/206 during somite differentiation. MicroRNA inhibition in chick embryos leads to increased BAF60a or BAF60b levels, a concomitant switch in BAF/Brg1 subunit composition and delayed myogenesis. The phenotypes are mimicked by sustained BAF60a or BAF60b expression and are rescued by morpholino knockdown of BAF60a or BAF60b. This suggests that myomiRs contribute to select BAF60c for incorporation into the Brg1 complex by specifically targeting the alternative variants BAF60a and BAF60b during embryo myogenesis, and reveals that interactions between tissue-specific non-coding RNAs and chromatin remodeling factors confer robustness to mesodermal lineage determination.
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