Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development

Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks, but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely a result of increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double-mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and nonhistone proteins in oocyte development.

[1]  S. Haggarty,et al.  HDAC2 negatively regulates memory formation and synaptic plasticity , 2009, Nature.

[2]  P. Wassarman,et al.  Relationship between growth and meiotic maturation of the mouse oocyte. , 1976, Developmental biology.

[3]  M. Conti,et al.  Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. , 1996, Developmental biology.

[4]  Ali Shilatifard,et al.  Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. , 2006, Annual review of biochemistry.

[5]  L. Liang,et al.  Coordinate expression of the three zona pellucida genes during mouse oogenesis. , 1995, Development.

[6]  M. Bartolomei,et al.  Metastasis Tumor Antigen 2 (MTA2) Is Involved in Proper Imprinted Expression of H19 and Peg3 During Mouse Preimplantation Development1 , 2010, Biology of reproduction.

[7]  E. Olson,et al.  Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development , 2009, Proceedings of the National Academy of Sciences.

[8]  A. Shilatifard,et al.  Covalent modifications of histones during development and disease pathogenesis , 2007, Nature Structural &Molecular Biology.

[9]  Michael Berger,et al.  Apoptosis - the p53 network , 2003, Journal of Cell Science.

[10]  O. Dovey,et al.  Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation , 2010, Proceedings of the National Academy of Sciences.

[11]  G. Moore,et al.  Transcription of the mouse oocyte genome. , 1978, Biology of reproduction.

[12]  S. Kageyama,et al.  Alterations in epigenetic modifications during oocyte growth in mice. , 2007, Reproduction.

[13]  J. Taylor‐Papadimitriou,et al.  Functional Analysis of the Transcription Supplemental Material , 2007 .

[14]  P. Freemont,et al.  Human PLU-1 Has Transcriptional Repression Properties and Interacts with the Developmental Transcription Factors BF-1 and PAX9* , 2003, Journal of Biological Chemistry.

[15]  J. Lis,et al.  Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase on heat shock genes. , 2004, Molecular cell.

[16]  R. Schultz,et al.  Histone deacetylase 1 (HDAC1) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. , 2008, Developmental biology.

[17]  D. Andrews,et al.  Bcl‐xL/Bcl‐2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry , 2003, The EMBO journal.

[18]  P. Wassarman,et al.  An upstream region of the mouse ZP3 gene directs expression of firefly luciferase specifically to growing oocytes in transgenic mice. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Koji Sugiura,et al.  Mouse Oocyte Control of Granulosa Cell Development and Function: Paracrine Regulation of Cumulus Cell Metabolism , 2009, Seminars in reproductive medicine.

[20]  Stuart L Schreiber,et al.  Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. , 2002, Chemistry & biology.

[21]  A. Strasser,et al.  Bim: a novel member of the Bcl‐2 family that promotes apoptosis , 1998, The EMBO journal.

[22]  X. Wang,et al.  DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T. Kouzarides,et al.  Regulation of E2F1 activity by acetylation , 2000, The EMBO journal.

[24]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[25]  E. Cho,et al.  Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. , 2000, Genes & development.

[26]  M. Grunstein.  Histone acetylation in chromatin structure and transcription , 1997, Nature.

[27]  S. Minucci,et al.  Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer , 2006, Nature Reviews Cancer.

[28]  Fanyi Zeng,et al.  Transcript profiling during preimplantation mouse development. , 2004, Developmental biology.

[29]  Xiao-Fan Wang,et al.  HDAC6 is a microtubule-associated deacetylase , 2002, Nature.

[30]  R. Schultz,et al.  RNAi in mouse oocytes and preimplantation embryos: effectiveness of hairpin dsRNA. , 2001, Biochemical and biophysical research communications.

[31]  E. Olson,et al.  Epigenetic control of skull morphogenesis by histone deacetylase 8. , 2009, Genes & development.

[32]  E. Olson,et al.  The many roles of histone deacetylases in development and physiology: implications for disease and therapy , 2009, Nature Reviews Genetics.

[33]  R. Young,et al.  Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. , 1998, Molecular cell.

[34]  F. Aoki,et al.  Regulation of transcriptional activity during the first and second cell cycles in the preimplantation mouse embryo. , 1997, Developmental biology.

[35]  E. Seto,et al.  Lysine acetylation: codified crosstalk with other posttranslational modifications. , 2008, Molecular cell.

[36]  S. Schreiber,et al.  A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p , 1996, Science.

[37]  C. Seiser,et al.  Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. , 2009, The International journal of developmental biology.

[38]  D. Albertini,et al.  Oogenesis: Prospects and challenges for the future , 2008, Journal of cellular physiology.

[39]  R. Schultz,et al.  Transcript profiling during mouse oocyte development and the effect of gonadotropin priming and development in vitro. , 2005, Developmental biology.

[40]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[41]  Yi Tang,et al.  Acetylation Is Indispensable for p53 Activation , 2008, Cell.

[42]  Delin Chen,et al.  Deacetylation of p53 modulates its effect on cell growth and apoptosis , 2000, Nature.

[43]  D. Vaux.  Immunopathology of apoptosis —introduction and overview , 2004, Springer Seminars in Immunopathology.

[44]  D. O’Carroll,et al.  Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression , 2002, The EMBO journal.

[45]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[46]  K. Wassarman,et al.  Zp3–cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line , 1997, Current Biology.

[47]  K. Sugiura,et al.  Granulosa Cell Ligand NPPC and Its Receptor NPR2 Maintain Meiotic Arrest in Mouse Oocytes , 2010, Science.

[48]  Martin M. Matzuk,et al.  MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing , 2010, PLoS biology.

[49]  Bert W O'Malley,et al.  GCNF‐dependent repression of BMP‐15 and GDF‐9 mediates gamete regulation of female fertility , 2003, The EMBO journal.

[50]  D. Chao,et al.  BCL-2 family: regulators of cell death. , 1998, Annual review of immunology.

[51]  R. van den Hurk,et al.  Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. , 2005, Theriogenology.

[52]  Xiaoxia Qi,et al.  Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. , 2007, Genes & development.

[53]  D. Mottershead,et al.  Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. , 2005, Reproduction.

[54]  S. Berger.  The complex language of chromatin regulation during transcription , 2007, Nature.

[55]  A. Levine,et al.  Functions of the MDM2 oncoprotein , 1999, Cellular and Molecular Life Sciences CMLS.

[56]  J. Lewis,et al.  An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. , 1989, Journal of reproduction and fertility.

[57]  J. Mehnert,et al.  Histone Deacetylase Inhibitors: Biology and Mechanism of Action , 2007, Cancer journal.

[58]  Thomas A. Milne,et al.  WDR5 Associates with Histone H3 Methylated at K4 and Is Essential for H3 K4 Methylation and Vertebrate Development , 2005, Cell.

[59]  H. Kohler,et al.  Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. , 2010, Genes & development.

[60]  L. Tora,et al.  TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte. , 2009, Genes & development.

[61]  D. Mottershead,et al.  Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function. , 2005, Reproduction.

[62]  Paul Tempst,et al.  PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. , 2007, Molecular cell.

[63]  J. Epstein,et al.  Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. , 2010, Developmental cell.

[64]  Yoshiharu Kawaguchi,et al.  MDM2–HDAC1‐mediated deacetylation of p53 is required for its degradation , 2002, The EMBO journal.

[65]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[66]  J. Eppig,et al.  Transcriptional activity of the mouse oocyte genome: companion granulosa cells modulate transcription and chromatin remodeling. , 2001, Developmental biology.

[67]  Jessica E. Bolden,et al.  Anticancer activities of histone deacetylase inhibitors , 2006, Nature Reviews Drug Discovery.

[68]  A. Peters,et al.  Mechanisms of transcriptional repression by histone lysine methylation. , 2009, The International journal of developmental biology.