YB-1 regulation of the human and rat gelatinase A genes via similar enhancer elements.
YB-1 regulation of the human and rat gelatinase A genes via similar enhancer elements.
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发表时间：
1999-12
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通讯作者：
P. Mertens;M. Alfonso-Jaume;K. Steinmann;D. Lovett
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作者：
P. Mertens;M. Alfonso-Jaume;K. Steinmann;D. Lovett
实验和临床研究强烈表明，明胶酶A在肾小球损伤和硬化症的演变中起着核心作用。人和大鼠明胶酶A基因的5'侧区序列与基质金属蛋白酶基因家族的其他成员没有相似之处，并以独特的方式受到调节。人和大鼠明胶酶A基因包括显著同源区域（r2人；RE-1大鼠），这些区域已被证明是有效的顺式转录激活因子。大鼠RE-1序列与发育调节的转录因子AP2和YB-1特异性相互作用，导致明胶酶a转录的协同激活。虽然人类r2序列特异性地与AP2相互作用（Mol Cell Biol 10: 6524-6532, 1990），但没有明确的证据表明该序列中存在典型的YB-1结合位点（Y-box）。该研究表明，尽管r2元件中缺乏典型的Y-box序列，但YB-1和AP2特异性地与r2相互作用，产生人类明胶酶a基因的协同转激活。由此可见，r2元件是RE-1元件的保守功能类似物，AP2和YB-1的相互作用支配着人明胶酶A基因的表达。
Experimental and clinical studies strongly suggest that gelatinase A plays a central role in the evolution of glomerular injury and sclerosis. The sequences of the 5' flanking regions of the human and rat gelatinase A genes do not share similarities with other members of the matrix metalloproteinase gene family and are regulated in a distinctive manner. The human and rat gelatinase A genes include regions of significant homology (r2 human; RE-1 rat), which have been shown to act as potent cis-activators of transcription. The rat RE-1 sequence interacts specifically with the developmentally regulated transcription factors AP2 and YB-1, resulting in a synergistic activation of gelatinase A transcription. Although the human r2 sequence specifically interacts with AP2 (Mol Cell Biol 10: 6524-6532, 1990), there is no clear evidence for the presence of a canonical YB-1 binding site (Y-box) within this sequence. This study demonstrates, despite the absence of a canonical Y-box sequence in the r2 element, that YB-1 and AP2 specifically interact with r2, yielding synergistic transactivation of the human gelatinase A gene. It is concluded that the r2 element is the conserved functional analog of the RE-1 element, and that interactions of AP2 and YB-1 govern human gelatinase A gene expression.