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Molecular Mechanisms of Male Sex Determination

The Enigma of SRY

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DNA Conformation and Transcription

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

The human testis-determining gene Sry, a single-copy gene on the short arm of the Y chromosome, encodes a high-mobility-group (HMG) box, a DNA-bending motif conserved among architectural transcription factors. The SRY-DNA complex exhibits a dramatic reorganization of the double helix. Although Sry-related Sox genes are of broad interest in relation to development, the mechanistic role of SRY in gene regulation has remained enigmatic. It is not known whether the HMG box is the sole functional domain of the protein. Additional unresolved issues include identification of target genes and interacting proteins. Although sex-reversal mutations commonly impair DNA binding, this correlation is not rigorous and does not exclude alternative regulatory mechanisms, such as possible SRY-directed RNA splicing. New studies of transgenic XX mice expressing chimeric SRY proteins suggest a powerful methodology to investigate structure-function relationships. Progress may benefit from genetic, genomic- and proteomic-based technologies to delineate the downstream pathway of SRY.

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  1. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA

    Michael A. Weiss

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Weiss, M.A. (2005). Molecular Mechanisms of Male Sex Determination. In: DNA Conformation and Transcription. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-29148-2_12

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