Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Cell Tissue Res. 2011 Jul;345(1):137-48. doi: 10.1007/s00441-011-1182-x. Epub 2011 Jun 7.
The mammalian SWI/SNF chromatin remodeling complexes play essential roles in cell cycle control through the transcriptional regulation of cell-cycle-specific genes. These complexes depend on the energy of ATP hydrolysis provided by the BRG1 or BRM catalytic subunit. They contain seven or more noncatalytic subunits, some being constitutive components, with others having paralogs that assemble in a combinatory manner producing different SWI/SNF-related complexes with specific functions. ARID1A and ARID1B are mutually exclusive subunits of the BAF complex. The specific presence of these subunits in the complex has been demonstrated to determine whether SWI/SNF functions as a corepressor (ARID1A) or as a coactivator (ARID1B) of the cell cycle genes. Our aim has been to analyze the relevance of the ARID1 subunits in development. We have compared the patterns of expression of these two genes through various mouse embryonic stages. Arid1a is expressed widely and intensively, whereas Arid1b is poorly transcribed and expressed in selected regions. Moreover, ARID1A and ARID1B present different kinetics of expression in the cell cycle. ARID1A accumulates in G0 and is downregulated throughout the cell cycle phases but is completely eliminated during mitosis, whereas ARID1B is expressed at comparable levels at all phases, even during mitosis. These kinetics probably affect the incorporation patterns of the ARID1 proteins to the complex and hence modulate SWI/SNF activity during proliferation and arrest.
哺乳动物的 SWI/SNF 染色质重塑复合物通过细胞周期特异性基因的转录调控,在细胞周期控制中发挥着重要作用。这些复合物依赖于 BRG1 或 BRM 催化亚基提供的 ATP 水解能量。它们包含七个或更多的非催化亚基,有些是组成性成分,有些则具有以组合方式组装的同源物,产生具有特定功能的不同 SWI/SNF 相关复合物。ARID1A 和 ARID1B 是 BAF 复合物的互斥亚基。已经证明这些亚基在复合物中的特定存在决定了 SWI/SNF 是作为细胞周期基因的核心抑制剂(ARID1A)还是共激活剂(ARID1B)发挥作用。我们的目的是分析 ARID1 亚基在发育中的相关性。我们通过各种小鼠胚胎阶段比较了这两个基因的表达模式。Arid1a 广泛且强烈表达,而 Arid1b 转录水平低,仅在特定区域表达。此外,ARID1A 和 ARID1B 在细胞周期中的表达动力学不同。ARID1A 在 G0 期积累,并在整个细胞周期各相中下调,但在有丝分裂期间完全消除,而 ARID1B 在所有相中表达水平相当,甚至在有丝分裂期间也是如此。这些动力学可能会影响 ARID1 蛋白与复合物的结合模式,从而在增殖和停滞期间调节 SWI/SNF 活性。