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哺乳动物SWI/SNF复合物的多样性与特异性

Diversity and specialization of mammalian SWI/SNF complexes.

作者信息

Wang W, Xue Y, Zhou S, Kuo A, Cairns B R, Crabtree G R

机构信息

Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, California 94305-5428, USA.

出版信息

Genes Dev. 1996 Sep 1;10(17):2117-30. doi: 10.1101/gad.10.17.2117.

DOI:10.1101/gad.10.17.2117
PMID:8804307
Abstract

The SWI/SNF complex in yeast facilitates the function of transcriptional activators by opposing chromatin-dependent repression of transcription. We demonstrate that in mammals SWI/SNF complexes are present in multiple forms made up of 9-12 proteins that we refer to as BRG1-associated factors (BAFs) ranging from 47 to 250 kD. We have isolated cDNAs for human BAF155, BAF170, and BAF60. BAF155 and BAF170 are encoded by separate genes that are both homologs of yeast SWI3. Both contain a region of similarity to the DNA binding domain of myb, but lack the basic residues known to be necessary for interaction with DNA. The two SWI3 homologs copurify on antibody columns specific for either BAF155 or BAF170, indicating that they are in the same complex. BAF60 is encoded by a novel gene family. An open reading frame from yeast, which is highly homologous, encodes the previously uncharacterized 73-kD subunit of the yeast SWI/SNF complex required for transcriptional activation by the glucocorticoid receptor (Cairns et al., this issue). BAF60a is expressed in all tissues examined, whereas BAF60b and BAF60c are expressed preferentially in muscle and pancreas, respectively. BAF60a is present within the 2000-kD BRG1 complex, whereas BAF60b is in a distinct complex that shares some but not all subunits with the BRG1 complex. The observed similarity between mammalian BAF190, BAF170, BAF155, BAF60, and BAF47 and yeast SNF2/SWI2, SWI3, SWI3, SWP73, and SNF5, respectively, underscores the similarity of the mammalian and yeast complexes. However, the complexes in mammals are more diverse than the SWI/SNF complex in yeast and are likely dedicated to developmentally distinct functions.

摘要

酵母中的SWI/SNF复合物通过对抗染色质依赖性的转录抑制来促进转录激活因子的功能。我们证明,在哺乳动物中,SWI/SNF复合物以多种形式存在,由9 - 12种蛋白质组成,我们将其称为BRG1相关因子(BAFs),分子量范围从47到250 kD。我们已经分离出人类BAF155、BAF170和BAF60的cDNA。BAF155和BAF170由不同的基因编码,这两个基因都是酵母SWI3的同源物。它们都含有一段与myb DNA结合结构域相似的区域,但缺少已知与DNA相互作用所必需的碱性残基。这两个SWI3同源物在针对BAF155或BAF170的抗体柱上共同纯化,表明它们存在于同一复合物中。BAF60由一个新的基因家族编码。酵母中的一个开放阅读框与BAF60高度同源,它编码酵母SWI/SNF复合物中先前未被鉴定的73 - kD亚基,该亚基是糖皮质激素受体转录激活所必需的(凯恩斯等人,本期)。BAF60a在所有检测的组织中均有表达,而BAF60b和BAF60c分别优先在肌肉和胰腺中表达。BAF60a存在于2000 - kD的BRG1复合物中,而BAF60b存在于一个与BRG1复合物有部分但并非全部亚基相同的独特复合物中。观察到的哺乳动物BAF190、BAF170、BAF155、BAF60和BAF47与酵母SNF2/SWI2、SWI3、SWI3、SWP73和SNF5之间的相似性,突出了哺乳动物和酵母复合物的相似性。然而,哺乳动物中的复合物比酵母中的SWI/SNF复合物更加多样化,并且可能具有不同的发育功能。

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