REGULATION OF EXPRESSION OF THE TYPE-I COLLAGEN GENES

REGULATION OF EXPRESSION OF THE TYPE-I COLLAGEN GENES
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DOI:
10.1002/ajmg.1320450203
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发表时间:
1993-01-15
期刊:
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子:
--
通讯作者:
BORNSTEIN, P
BORNSTEIN, P
中科院分区:
其他
文献类型:
--
作者:
SLACK, JL;LISKA, DJ;BORNSTEIN, P

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I型胶原基因内含子区和5'侧区dna -蛋白相互作用的鉴定和功能分析已经开始定义一系列调节这些基因转录的顺式元件和反式作用因子。诸如此类的研究最终将有望阐明负责α 1和α 2基因协调转录的机制,这是胶原蛋白研究领域的一个核心问题。虽然确定dna -蛋白质结合位点相对简单,但解释这种相互作用的功能重要性可能非常复杂。此外,虽然特定结合位点的突变或缺失可能会改变转染到培养细胞中的构建体的功能活性,但不能保证类似的变化会在体内产生相同的效果,因为整个基因位点存在于其原生染色体环境中。尽管如此,这些类型的体外研究为定义和分离控制alpha1和alpha2基因表达的转录因子提供了目前最好的方法。最终,有必要在体内确定的系统中测试这些因子(及其各自的顺式元件)的活性。
The identification and functional analysis of DNA-protein interactions in the intronic and 5' flanking regions of the type I collagen genes has begun to define a series of cis-elements and trans-acting factors which regulate transcription of these genes. Studies such as these will eventually be expected to elucidate the mechanisms responsible for coordinate transcription of the alpha1 and alpha2 genes, a question which remains central to the field of collagen research. Although it is relatively straightforward to define sites of DNA-protein binding, interpretation of the functional importance of such interactions can be extremely complex. Furthermore, while mutation or deletion of a particular binding site may alter the functional activity of a construct transfected into cultured cells, there is no guarantee that a similar change will have the same effect in vivo, where the entire gene locus is present in its native chromosomal context. Nevertheless, these kinds of in vitro studies offer the best current approach to defining and isolating transcription factors that control expression of the alpha1 and alpha2 genes. Ultimately, it will be necessary to test the activity of such factors (and their respective cis-elements) in defined systems in vivo.