Family of SRY/Sox proteins is involved in the regulation of the mouseMsh4 (MutS homolog 4) gene expression

The eukaryotic MutHLS-like system plays a crucial role in both mitosis and meiosis. Until now, a number of works have focused on the function of MutS and MutL homologs during mismatch DNA repair. Nevertheless, little is known about the role of these proteins during meiosis. MSH4 is a meiosis specific protein that is necessary for meiotic recombination in Saccharomyces cerevisiae. The human MSH4 protein is only found in testis and ovary. It is involved first in synapsis and second during recombination together with MLH1 (MutL Homolog 1). Here, we report the identification of the mouse Msh4 gene that is located on chromosome 3. We examined the expression of mMsh4 in testes of increasing developmental age and in elutriated germ cells. The pattern of expression during spermatogenesis is consistent with a role for MSH4 both during zygonema and pachynema. We demonstrated a promoter activity of the mMsh4 5'-flanking region by cell transfection experiments with a luciferase reporter gene. We found several SRY/Sox binding sites in this region and co-transfection experiments showed that SRY could down regulate mMsh4 promoter transcriptional activity. We propose that the regulation of mMsh4 expression could be one of the reasons for the persistence of SRY and/or SRY-related proteins in adult testis.