Slack J L, Liska D J, Bornstein P
Department of Biochemistry and Medicine, University of Washington, Seattle 98195.
Am J Med Genet. 1993 Jan 15;45(2):140-51. doi: 10.1002/ajmg.1320450203.
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 alpha 1 and alpha 2 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 alpha 1 and alpha 2 genes. Ultimately, it will be necessary to test the activity of such factors (and their respective cis-elements) in defined systems in vivo.
对I型胶原基因内含子和5'侧翼区域中DNA-蛋白质相互作用的鉴定和功能分析，已开始确定一系列调控这些基因转录的顺式元件和反式作用因子。诸如此类研究最终有望阐明负责α1和α2基因协同转录的机制，这一问题仍是胶原研究领域的核心问题。虽然确定DNA-蛋白质结合位点相对简单，但解释此类相互作用的功能重要性可能极其复杂。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，但不能保证在体内（整个基因座存在于其天然染色体环境中）发生类似变化时会有相同的效果。然而，这些体外研究提供了目前定义和分离控制α1和α2基因表达的转录因子的最佳方法。最终，有必要在体内特定系统中测试此类因子（及其各自的顺式元件）的活性。
