NUCLEOPROTEIN COMPLEXES THAT REGULATE GENE-EXPRESSION IN ADIPOCYTE DIFFERENTIATION - DIRECT PARTICIPATION OF C-FOS

NUCLEOPROTEIN COMPLEXES THAT REGULATE GENE-EXPRESSION IN ADIPOCYTE DIFFERENTIATION - DIRECT PARTICIPATION OF C-FOS
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DOI:
10.1016/0092-8674(87)90621-0
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发表时间:
1987-06-19
期刊:
影响因子:
64.5
通讯作者:
SPIEGELMAN, BM
SPIEGELMAN, BM
中科院分区:
生物学1区
文献类型:
--
作者:
DISTEL, RJ;RO, HS;SPIEGELMAN, BM

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脂肪细胞分化伴随着许多新基因的转录激活,包括一种假定的脂质结合蛋白,称为脂肪细胞 P2 (aP2)。 aP2 基因在其转录起始点 5'' 处包含一个 124 个碱基的调节元件 (FSE2)。该元件以序列特异性和分化依赖性方式结合核因子,这通过凝胶阻滞测定中改变的迁移率来确定。启动子连接的转染测定的缺失分析以及这些构建体在具有合成FSE2元件的细胞中的竞争表明反式作用因子与该区域结合并充当前脂肪细胞中aP2基因活性的负调节因子。 c-fos 似乎直接参与这种核蛋白复合物,c-fos 抗体能够破坏因子与 FSE2 序列的特异性结合,但不会破坏来自其他几个基因的因子结合序列,这证明了这一点。 c-fos 抗体通过 UV 交联特异性免疫沉淀与 FSE2 DNA 共价结合的蛋白质复合物。
Adipocyte differentiation is accompanied by the transcriptional activation of many new genes, including a putative lipid-binding protein termed adipocyte P2 (aP2). The aP2 gene contains a regulatory element (FSE2) 124 bases 5'' to its start of transcription. This element binds nuclear factors in sequence-specific and differentiation-dependent fashion as determined by altered mobility in gel retardation assays. Deletion analysis of promotor-linked transfection assays and competition of these constructions in cells with a synthetic FSE2 element suggest that trans-acting factors bind to this region and act as negative regulators of aP2 gene activity in preadipocytes. c-fos appears to participate directly in this nucleoprotein complex, as demonstrated by the ability of antibodies to c-fos to disrupt specific binding of factors to the FSE2 sequence but not to factor-binding sequences from several other genes. Antibodies to c-fos specifically immunoprecipitate protein complexes covalently bound to FSE2 DNA via UV cross-linking.