Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis - Role of a YY-1 factor-binding negative enhancer
Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis - Role of a YY-1 factor-binding negative enhancer
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DOI：
10.1074/jbc.272.9.5899
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发表时间：
1997-02-28
影响因子：
4.8
通讯作者：
Avadhani, NG
中科院分区：
文献类型：
--
作者：
Basu, A;Lenka, N;Avadhani, NG
小鼠细胞色素氧化酶(COX)Vb启动子含有三个部分或全部与YY-1和GTG因子结合的序列基序和一个位于-480和-390之间的Carg盒，这三个基序分别刺激TKCAT启动子的转录，并与肝脏和分化的C2C12核提取物明显不同的蛋白结合，这些基序与下游的侧翼序列-378到-320一起抑制了异源启动子、胸苷激酶-氯霉素乙酰转移酶(TKCAT)和COXIV/CAT的转录活性。在诱导C2C12细胞发生过程中，TKCAT和COXIV/CAT的转录活性都被诱导了3-4倍下游的Carg类基序与转录因子YY-1结合，上游的YY-1类基序与一个未知因子结合。表达完整的YY-1而不是缺乏DNA结合区的GO抑制转录活性。针对类Carg基序的突变消除了负增强子的抑制作用和在肌细胞分化过程中启动子的诱导性。我们的结果提示，负性增强子的活性可能决定了COX VB基因在不同组织中的表达水平。
The mouse cytochrome oxidase (COX) Vb promoter contains three sequence motifs with partial or full consensus for YY-1 and GTG factor binding and a CArG box, located between positions -480 and -390, Individually, all three motifs stimulated transcription of the TKCAT promoter, and bound distinctly different proteins from the liver and differentiated C2C12 nuclear extracts, Collectively, these motifs, together with the downstream flanking sequence, -378 to -320, suppressed the transcription activity of heterologous promoters, thymidine kinase-chloramphenicol acetyltransferase (TKCAT) and COXIV/CAT, The transcription activities of both TKCAT and COXIV/CAT constructs were induced 3-4-fold during induced myogenesis of C2C12 cells, The downstream CArG-like motif binds transcription factor YY-1, while the upstream YY-1-like motif binds to a yet unidentified factor. Go-expression with intact YY-1, but not that lacking the DNA binding domain suppressed the transcriptional activity. Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation. Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissues.