Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping.

Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping.
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通过辐射杂交和断点作图分析人类松弛素 H1 和 H2 基因的 5 上游区域及其在染色体 9p24.1 上的染色体定位。

DOI:
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发表时间:
1999
影响因子:
3.5
通讯作者:
G. Bryant
G. Bryant
中科院分区:
医学3区
文献类型:
--
作者:
J. Garibay;K. Csiszȧr;M. Fox;S. Povey;G. Bryant

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松弛素是已知的内分泌和自分泌/旁分泌激素,在生殖中起主要作用。在人类中有两个松弛素基因,H1和H2,它们在其编码区内共享90%的序列同源性。两个高度同源和生物活性的人类松弛素的生物学和进化意义是未知的。为了更好地理解这两个基因差异表达的调控机制,并深入了解它们在早产胎膜早破中的作用,我们研究了它们的5 '上游区域的特性,并通过辐射杂交和断点定位将它们定位到同一染色体9p24.1位点。这些松弛素基因的5'端可分为近端高度同源区段和远端非同源区段。在近端区域内包含两个基因共同的几个推定的调控元件,表明类似的调控机制。松弛素基因在同一染色体位点的聚类表明,这些基因可能是在一个共同的调控。另一方面,单个松弛素基因也可能存在不同的基因特异性调控,因为在它们的5'端鉴定了对每个基因特异的顺式元件。此外,在其5 '-上游序列的远端区域观察到的差异可能提供充当基因特异性转录调节子的结构特征。由于这两个基因在其编码区和侧翼区高度同源,在其5'末端的远端区域的分歧可能是重要的,在这些基因的调节和参与早产的病理。
Relaxins are known endocrine and autocrine/paracrine hormones that play a major role in reproduction. In the human there are two relaxin genes, H1 and H2 which share 90% sequence homology within their coding region. The biological and evolutionary significance of two highly homologous and biologically active human relaxins is unknown. In order to achieve a better understanding of the regulatory mechanisms involved in the differential expression of these two genes and to gain insight into their role(s) in the preterm premature rupture of the membranes, we have investigated the properties of their 5'-upstream regions and mapped them both by radiation hybrid and breakpoint mapping into the same chromosome 9p24.1 locus. The 5' ends of these relaxin genes could be divided into a proximal highly homologous segment and a distal non-homologous region. Within the proximal region are contained several putative regulatory elements common to both genes, suggesting a similar regulatory mechanism. The clustering of the relaxin genes within the same chromosomal locus suggests that these genes may be under a common regulation. On the other hand, a distinct gene-specific regulation may also exist for the individual relaxin genes since cis elements specific to each gene were identified at their 5' ends. Moreover, the observed divergence at the distal region of their 5'-upstream sequences may provide the structural features that act as gene-specific transcription regulators. Since the two genes are highly homologous in both their coding and flanking regions, the divergence at the distal region of their 5' ends may be important in the regulation of these genes and in their involvement in the pathology of preterm birth.
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