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

Relaxins are known endocrine and autocrine/paracrine hormones that play a m ajor role in reproduction. In the human there are two relaxin genes, H1 and H2 which share 90% sequence homology within their coding region. The biolo gical and evolutionary significance of two highly homologous and biological ly active human relaxins is unknown. In order to achieve a better understan ding of the regulatory mechanisms involved in the differential expression o f these two genes and to gain insight into their role(s) in the preterm pre mature rupture of the membranes, we have investigated the properties of the ir 5'-upstream regions and mapped them both by radiation hybrid and breakpo int mapping into the same chromosome 9p24.1 locus. The 5' ends of these rel axin genes could be divided into a proximal highly homologous segment and a distal non-homologous region. Within the proximal region are contained sev eral putative regulatory elements common to both genes, suggesting a simila r regulatory mechanism. The clustering of the relaxin genes within the same chromosomal locus suggests that these genes may be under a common regulati on. On the other hand, a distinct gene-specific regulation may also exist f or the individual relaxin genes since cis elements specific to each gene we re identified at their 5' ends. Moreover, the observed divergence at the di stal region of their 5'-upstream sequences may provide the structural featu res that act as gene-specific transcription regulators. Since the two genes are highly homologous in both their coding and flanking regions, the diver gence at the distal region of their 5' ends may be important in the regulat ion of these genes and in their involvement in the pathology of preterm bir th.