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  • The EMBO Journal (2004) 23, 3336 - 3345
  • doi:10.1038/sj.emboj.7600352

Published online: 5 August 2004

Regulation of human SRY subcellular distribution by its acetylation/deacetylation

Laurie Thevenet1, Catherine Méjean1, Brigitte Moniot1, Nathalie Bonneaud1, Nathalie Galéotti2, Gudrun Aldrian-Herrada3, Francis Poulat1, Philippe Berta1, Monsef Benkirane4 and Brigitte Boizet-Bonhoure1

  1. Human Molecular Genetics Group, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France
  2. Laboratoire de Génomique Fonctionnelle, CNRS UPR 2580, Montpellier, France
  3. Centre de Biochimie Structurale, Université Montpellier I, Montpellier, France
  4. Laboratory of Molecular Virology, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France

Correspondence to:

Brigitte Boizet-Bonhoure, Institut de Génétique Humaine, CNRS UPR 1142, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France. Tel.: +33 4 99 61 99 40; Fax: +33 4 99 61 99 42; E-mail: boizet@igh.cnrs.fr

Received 20 February 2004; Accepted 8 July 2004

SRY, a Y chromosome-encoded DNA-binding protein, is required for testis organogenesis in mammals. Expression of the SRY gene in the genital ridge is followed by diverse early cell events leading to Sertoli cell determination/differentiation and subsequent sex cord formation. Little is known about SRY regulation and its mode of action during testis development, and direct gene targets for SRY are still lacking. In this study, we demonstrate that interaction of the human SRY with histone acetyltransferase p300 induces the acetylation of SRY both in vitro and in vivo at a single conserved lysine residue. We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. Finally, by analysing p300 and HDAC3 expression profiles during both human or mouse gonadal development, we suggest that acetylation and deacetylation of SRY may be important mechanisms for regulating SRY activity during mammalian sex determination.

  • Keywords:

    • acetylation,
    • mammals,
    • nuclear localisation,
    • sex determination,
    • SRY