Identification of regulatory regions which confer muscle-specific gene expression
Identification of regulatory regions which confer muscle-specific gene expression
复制标题
DOI：
10.1006/jmbi.1998.1700
复制
发表时间：
1998-04-24
影响因子：
5.6
通讯作者：
Fickett, JW
中科院分区：
文献类型：
--
作者：
Wasserman, WW;Fickett, JW
对于许多新测序的基因，对推定蛋白质的序列分析无法提供功能方面的线索。能够在基因组中鉴定赋予未表征基因的时间和空间表达模式的调控区将是有益的。另外，鉴定已知表达模式的基因内的调节区域而不进行现在所需的昂贵且耗时的实验室研究将是有利的。为了实现这些目标，必须将过去15年进行的大量案例研究收集到表达预测模型中。对骨骼肌中表达的基因的广泛研究已经确定了与调控元件结合以控制基因表达的特异性转录因子。然而，这些因子的潜在结合位点以足够的频率出现，以至于很少发现没有一个基因的基因。实验确定的肌肉调控序列的分析表明，肌肉的表达需要多个元素的紧密接近。生成具有预测能力的模型，用于识别这些肌肉特异性调节模块。系统发育足迹法，即确定远亲物种之间保守的序列，补充了统计预测。通过使用逻辑回归分析，该模型有望很容易修改，以利用额外的因素，合作规则和间距限制的说明。(C)出版社：Academic Press Limited。
For many newly sequenced genes, sequence analysis of the putative protein yields no clue on function. It would be beneficial to be able to identify in the genome the regulatory regions that confer temporal and spatial expression patterns for the uncharacterized genes. Additionally, it would be advantageous to identify regulatory regions within genes of known expression pattern without performing the costly and time consuming laboratory studies now required. To achieve these goals, the wealth of case studies performed over the past 15 years will have to be collected into predictive models of expression. Extensive studies of genes expressed in skeletal muscle have identified specific transcription factors which bind to regulatory elements to control gene expression. However, potential binding sites for these factors occur with sufficient frequency that it is rare for a gene to be found without one. Analysis of experimentally determined muscle regulatory sequences indicates that muscle expression requires multiple elements in close proximity. A model is generated with predictive capability for identifying these muscle-specific regulatory modules. Phylogenetic footprinting, the identification of sequences conserved between distantly related species, complements the statistical predictions. Through the use of logistic regression analysis, the model promises to be easily modified to take advantage of the elucidation of additional factors, cooperation rules, and spacing constraints. (C) 1998 Academic Press Limited.