New insights into SRY regulation through identification of 5' conserved sequences

Diana Gf Ross,Peter Koopman,Sigrid Lehnert,Josephine Bowles

doi:10.1186/1471-2199-9-85

Abstract

BackgroundSRY is the pivotal gene initiating male sex determination in most mammals, but how its expression is regulated is still not understood. In this study we derived novel SRY 5' flanking genomic sequence data from bovine and caprine genomic BAC clones.ResultsWe identified four intervals of high homology upstream of SRY by comparison of human, bovine, pig, goat and mouse genomic sequences. These conserved regions contain putative binding sites for a large number of known transcription factor families, including several that have been implicated previously in sex determination and early gonadal development.ConclusionOur results reveal potentially important SRY regulatory elements, mutations in which might underlie cases of idiopathic human XY sex reversal.

Highlights

Sex determining region on the Y chromosome (SRY) is the pivotal gene initiating male sex determination in most mammals, but how its expression is regulated is still not understood
The bacterial artificial chromosome (BAC) clone RP42-95D10 containing bovine SRY [17] was found by Southern blotting and polymerase chain reaction (PCR) to contain a 15 kb EcoR1 fragment harbouring SRY
We generated corresponding fragments of the goat SRY 5' region by PCR using as template a goat BAC clone containing SRY and known to cause female to male sex reversal in mice [18]

Summary

Introduction

SRY is the pivotal gene initiating male sex determination in most mammals, but how its expression is regulated is still not understood. Male sex determination in almost all mammals is directly caused by the correct expression and function of a single Y-linked gene, SRY[14]. A majority of gonadal dysgenesis cases cannot be attributed to mutations within or immediately 5' of SRY, or to any other gene known to have a role in sex determination. We hypothesise that this is because SRY's regulatory regions are uncharted, providing no means to check specific areas for mutation

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Conclusion