Regulation of human SRY subcellular distribution by its acetylation/deacetylation.

Human Molecular Genetics Group, Institut de Genetique Humaine, CNRS UPR 1142, Montpellier, France.
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.
Mesh Terms:
Acetylation, Acetyltransferases, Active Transport, Cell Nucleus, Animals, Cell Cycle Proteins, Cell Line, Cell Nucleus, DNA, DNA-Binding Proteins, Gene Expression Regulation, Gonads, Histone Acetyltransferases, Histone Deacetylases, Humans, Lysine, Male, Mice, Nuclear Proteins, Protein Binding, Sex-Determining Region Y Protein, Transcription Factors, p300-CBP Transcription Factors
EMBO J. Aug. 18, 2004; 23(16);3336-45 [PUBMED:15297880]
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