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PMID: 15297880 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 23 ·No. 16 ·2004-08-18 ·Pages 3336-45

Thevenet L, Méjean C, Moniot B, Bonneaud N, Galéotti N, Aldrian-Herrada G, Poulat F, Berta P, Benkirane M, Boizet-Bonhoure B

Abstract

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/metabolism Active Transport, Cell Nucleus Animals Cell Cycle Proteins/metabolism Cell Line Cell Nucleus/metabolism DNA/metabolism DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Gonads/embryology,metabolism Histone Acetyltransferases Histone Deacetylases/metabolism Humans Lysine/genetics,metabolism Male Mice Nuclear Proteins/genetics,metabolism Protein Binding Sex-Determining Region Y Protein Transcription Factors/genetics,metabolism p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Nuclear Proteins SRY protein, human Sex-Determining Region Y Protein Sry protein, mouse Transcription Factors DNA Acetyltransferases Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor Histone Deacetylases histone deacetylase 3 Lysine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Thevenet Laurie
Human Molecular Genetics Group, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France.
Méjean Catherine
Moniot Brigitte
Bonneaud Nathalie
Galéotti Nathalie
Aldrian-Herrada Gudrun
Poulat Francis
Berta Philippe
Benkirane Monsef
Boizet-Bonhoure Brigitte
References (61)
61 references, click to expand
  1. Acetylation of the adenovirus-transforming protein E1A determines nuclear localization by disrupting association with importin-alpha.
    J Biol Chem. 2002 Oct 11;277(41):38755-63 PMID: 12161448
  2. Cooperation between complexes that regulate chromatin structure and transcription.
    Cell. 2002 Feb 22;108(4):475-87 PMID: 11909519
  3. Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1.
    Genes Dev. 2003 Mar 15;17(6):717-22 PMID: 12651889
  4. Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9.
    J Biol Chem. 2003 Jul 18;278(29):27224-9 PMID: 12732631
  5. Effects of trichostatin a, a histone deacetylase inhibitor, on mouse gonadal development in vitro.
    J Reprod Dev. 2004 Apr;50(2):227-35 PMID: 15118250
  6. Studies of acetylation and deacetylation in high mobility group proteins. Identification of the sites of acetylation in HMG-1.
    J Biol Chem. 1979 Nov 25;254(22):11577-83 PMID: 500660
  7. Genetic evidence equating SRY and the testis-determining factor.
    Nature. 1990 Nov 29;348(6300):448-50 PMID: 2247149
  8. Expression of a candidate sex-determining gene during mouse testis differentiation.
    Nature. 1990 Nov 29;348(6300):450-2 PMID: 2247150
  9. DNA binding activity of recombinant SRY from normal males and XY females.
    Science. 1992 Jan 24;255(5043):453-6 PMID: 1734522
  10. Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis.
    Am J Hum Genet. 1992 Nov;51(5):979-84 PMID: 1415266
  11. SRY, like HMG1, recognizes sharp angles in DNA.
    EMBO J. 1992 Dec;11(12):4497-506 PMID: 1425584
  12. Sex-reversing mutations affect the architecture of SRY-DNA complexes.
    EMBO J. 1994 Dec 15;13(24):6115-24 PMID: 7813448
  13. Nuclear localization of the testis determining gene product SRY.
    J Cell Biol. 1995 Mar;128(5):737-48 PMID: 7876301
  14. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function.
    Bioessays. 1995 May;17(5):423-30 PMID: 7786288
  15. In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import.
    EMBO J. 1995 Aug 1;14(15):3617-26 PMID: 7641681
  16. Targeting chromatin disruption: Transcription regulators that acetylate histones.
    Cell. 1996 Mar 22;84(6):817-9 PMID: 8601304
  17. Histone deacetylase: a regulator of transcription.
    Science. 1996 Apr 19;272(5260):371-2 PMID: 8602525
  18. Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds.
    Nat Genet. 1996 Sep;14(1):62-8 PMID: 8782821
  19. The transcriptional coactivators p300 and CBP are histone acetyltransferases.
    Cell. 1996 Nov 29;87(5):953-9 PMID: 8945521
  20. The CBP co-activator is a histone acetyltransferase.
    Nature. 1996 Dec 19-26;384(6610):641-3 PMID: 8967953
  21. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase.
    Cell. 1997 May 2;89(3):373-80 PMID: 9150137
  22. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function.
    Nature. 1997 Jun 12;387(6634):677-84 PMID: 9192892
  23. Histone acetylation in chromatin structure and transcription.
    Nature. 1997 Sep 25;389(6649):349-52 PMID: 9311776
  24. Two independent nuclear localization signals are present in the DNA-binding high-mobility group domains of SRY and SOX9.
    J Biol Chem. 1997 Oct 31;272(44):27848-52 PMID: 9346931
  25. Phosphorylation of an N-terminal motif enhances DNA-binding activity of the human SRY protein.
    J Biol Chem. 1998 Apr 3;273(14):7988-95 PMID: 9525897
  26. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.
    Cell. 1998 May 1;93(3):361-72 PMID: 9590171
  27. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene.
    Mol Cell Biol. 1998 Nov;18(11):6653-65 PMID: 9774680
  28. Regulation of LEF-1/TCF transcription factors by Wnt and other signals.
    Curr Opin Cell Biol. 1999 Apr;11(2):233-40 PMID: 10209158
  29. Mesonephric cell migration induces testis cord formation and Sertoli cell differentiation in the mammalian gonad.
    Development. 1999 Jul;126(13):2883-90 PMID: 10357932
  30. Histone deacetylase 1 can repress transcription by binding to Sp1.
    Mol Cell Biol. 1999 Aug;19(8):5504-11 PMID: 10409740
  31. Sry requires a CAG repeat domain for male sex determination in Mus musculus.
    Nat Genet. 1999 Aug;22(4):405-8 PMID: 10431249
  32. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.
    Nature. 1999 Sep 9;401(6749):188-93 PMID: 10490031
  33. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase.
    Cell. 1999 Sep 3;98(5):675-86 PMID: 10490106
  34. The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains.
    J Biol Chem. 1997 Mar 14;272(11):7167-72 PMID: 9054412
  35. HIV-1 tat transcriptional activity is regulated by acetylation.
    EMBO J. 1999 Nov 1;18(21):6106-18 PMID: 10545121
  36. Sry induces cell proliferation in the mouse gonad.
    Development. 2000 Jan;127(1):65-73 PMID: 10654601
  37. Identification of the transactivation domain of the transcription factor Sox-2 and an associated co-activator.
    J Biol Chem. 2000 Feb 11;275(6):3810-8 PMID: 10660531
  38. Acetylation: a regulatory modification to rival phosphorylation?
    EMBO J. 2000 Mar 15;19(6):1176-9 PMID: 10716917
  39. Expression and subcellular localization of SF-1, SOX9, WT1, and AMH proteins during early human testicular development.
    Dev Dyn. 2000 Mar;217(3):293-8 PMID: 10741423
  40. Acetylation of importin-alpha nuclear import factors by CBP/p300.
    Curr Biol. 2000 Apr 20;10(8):467-70 PMID: 10801418
  41. Acetylation of histones and transcription-related factors.
    Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59 PMID: 10839822
  42. CBP/p300 in cell growth, transformation, and development.
    Genes Dev. 2000 Jul 1;14(13):1553-77 PMID: 10887150
  43. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells.
    J Natl Cancer Inst. 2000 Aug 2;92(15):1210-6 PMID: 10922406
  44. Beta-catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator.
    Mol Cell Biol. 2000 Sep;20(18):6882-90 PMID: 10958684
  45. Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators.
    Dev Biol. 2000 Nov 15;227(2):239-55 PMID: 11071752
  46. Deacetylation of p53 modulates its effect on cell growth and apoptosis.
    Nature. 2000 Nov 16;408(6810):377-81 PMID: 11099047
  47. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin.
    Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):87-92 PMID: 11134513
  48. CREB-binding protein and histone deacetylase regulate the transcriptional activity of Kaposi's sarcoma-associated herpesvirus open reading frame 50.
    J Virol. 2001 Feb;75(4):1909-17 PMID: 11160690
  49. Steroidogenic factor-1 contributes to the cyclic-adenosine monophosphate down-regulation of human SRY gene expression.
    Biol Reprod. 2001 Mar;64(3):775-83 PMID: 11207191
  50. Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity.
    EMBO J. 2001 Apr 17;20(8):1984-92 PMID: 11296231
  51. Molecular evolution of Sry and Sox gene.
    Gene. 2001 May 30;270(1-2):161-9 PMID: 11404013
  52. Regulation of transcription factor YY1 by acetylation and deacetylation.
    Mol Cell Biol. 2001 Sep;21(17):5979-91 PMID: 11486036
  53. Coordination of a transcriptional switch by HMGI(Y) acetylation.
    Science. 2001 Aug 10;293(5532):1133-6 PMID: 11498590
  54. Duration of nuclear NF-kappaB action regulated by reversible acetylation.
    Science. 2001 Aug 31;293(5535):1653-7 PMID: 11533489
  55. Histone deacetylase 3 associates with and represses the transcription factor GATA-2.
    Blood. 2001 Oct 1;98(7):2116-23 PMID: 11567998
  56. Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5.
    J Biol Chem. 2001 Oct 5;276(40):37659-64 PMID: 11479297
  57. The C-terminal nuclear localization signal of the sex-determining region Y (SRY) high mobility group domain mediates nuclear import through importin beta 1.
    J Biol Chem. 2001 Dec 7;276(49):46575-82 PMID: 11535586
  58. Human sex reversal due to impaired nuclear localization of SRY. A clinical correlation.
    J Biol Chem. 2001 Dec 7;276(49):46480-4 PMID: 11641389
  59. Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription.
    Mol Cell. 2000 Nov;6(5):1059-66 PMID: 11106745
  60. Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor.
    Dev Biol. 2001 Dec 1;240(1):92-107 PMID: 11784049
  61. Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF.
    EMBO J. 2002 Dec 16;21(24):6811-9 PMID: 12486002
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600352
Published
2004-08-18
Epub
2004-00-05
Pages
3336-45
Language
English
Region
England
NLM ID
8208664
PMCID
PMC514523
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600352 PMC Full Text View journal details
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