EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice

ABSTRACT Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome.

[1]  Antoine H. F. M. Peters,et al.  Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa , 2013, Nature Structural &Molecular Biology.

[2]  A. Gyenesei,et al.  Transcriptome Profiling of the Murine Testis during the First Wave of Spermatogenesis , 2013, PloS one.

[3]  D. Wolgemuth,et al.  Bromodomain‐dependent stage‐specific male genome programming by Brdt , 2012, The EMBO journal.

[4]  K. Mochida,et al.  The Effect on Intracytoplasmic Sperm Injection Outcome of Genotype, Male Germ Cell Stage and Freeze-Thawing in Mice , 2010, PloS one.

[5]  Lin-Yu Lu,et al.  RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. , 2010, Developmental cell.

[6]  L. Reynard,et al.  The Multi-Copy Mouse Gene Sycp3-Like Y-Linked (Sly) Encodes an Abundant Spermatid Protein That Interacts with a Histone Acetyltransferase and an Acrosomal Protein1 , 2009, Biology of reproduction.

[7]  B. Cairns,et al.  Distinctive Chromatin in Human Sperm Packages Genes for Embryo Development , 2009, Nature.

[8]  J. Hayes,et al.  The H4 Tail Domain Participates in Intra- and Internucleosome Interactions with Protein and DNA during Folding and Oligomerization of Nucleosome Arrays , 2008, Molecular and Cellular Biology.

[9]  N. Yoshida,et al.  Azoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) gene , 2006, Proceedings of the National Academy of Sciences.

[10]  J. Garin,et al.  Post-meiotic Shifts in HSPA2/HSP70.2 Chaperone Activity during Mouse Spermatogenesis* , 2006, Journal of Biological Chemistry.

[11]  M. Iyo,et al.  Fyn Is Required for Haloperidol-induced Catalepsy in Mice* , 2006, Journal of Biological Chemistry.

[12]  M. Pazin,et al.  Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions , 2006, Science.

[13]  A. Gansmuller,et al.  Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. Sardet,et al.  A Novel Repressive E2F6 Complex Containing the Polycomb Group Protein, EPC1, That Interacts with EZH2 in a Proliferation-specific Manner* , 2005, Journal of Biological Chemistry.

[15]  J. Vonesch,et al.  Preparation, isolation and characterization of stage-specific spermatogenic cells for cellular and molecular analysis , 2004, Nature Methods.

[16]  M. Meistrich,et al.  Nucleoprotein Transitions During Spermiogenesis in Mice with Transition Nuclear Protein Tnp1 and Tnp2 Mutations1 , 2004, Biology of reproduction.

[17]  M. Griswold,et al.  The Murine Testicular Transcriptome: Characterizing Gene Expression in the Testis During the Progression of Spermatogenesis1 , 2004, Biology of reproduction.

[18]  G. Boissonneault,et al.  Transient DNA Strand Breaks During Mouse and Human Spermiogenesis: New Insights in Stage Specificity and Link to Chromatin Remodeling1 , 2004, Biology of reproduction.

[19]  J. Ausió,et al.  Histone H1 and the origin of protamines , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Song Tan,et al.  Structural and Functional Conservation of the NuA4 Histone Acetyltransferase Complex from Yeast to Humans , 2004, Molecular and Cellular Biology.

[21]  M. Péoc'h,et al.  Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer. , 2003, Molecular human reproduction.

[22]  C. Caron,et al.  Scientific Report , 2022 .

[23]  Song Tan,et al.  Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin. , 2003, Genes & development.

[24]  M. Meistrich,et al.  Roles of transition nuclear proteins in spermiogenesis , 2003, Chromosoma.

[25]  K. Failing,et al.  Expression of hyperacetylated histone H4 during normal and impaired human spermatogenesis , 2002, Andrologia.

[26]  D. Page,et al.  Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  K. Steger.  Haploid spermatids exhibit translationally repressed mRNAs , 2001, Anatomy and Embryology.

[28]  Y. Usson,et al.  Regulated hyperacetylation of core histones during mouse spermatogenesis: involvement of histone deacetylases. , 2000, European journal of cell biology.

[29]  J. Hoeijmakers,et al.  Histone ubiquitination and chromatin remodeling in mouse spermatogenesis. , 1999, Developmental biology.

[30]  Alan P. Wolffe,et al.  Disruption of Higher-Order Folding by Core Histone Acetylation Dramatically Enhances Transcription of Nucleosomal Arrays by RNA Polymerase III , 1998, Molecular and Cellular Biology.

[31]  N. Hecht,et al.  Molecular mechanisms of male germ cell differentiation , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[32]  R. Yanagimachi,et al.  Mouse oocytes injected with testicular spermatozoa or round spermatids can develop into normal offspring. , 1995, Development.

[33]  A. Ogura,et al.  Round spermatid nuclei injected into hamster oocytes from pronuclei and participate in syngamy. , 1993, Biology of reproduction.

[34]  C. Allis,et al.  Highly acetylated H4 is associated with histone displacement in rat spermatids , 1992, Molecular reproduction and development.

[35]  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.

[36]  D. Bazett-Jones,et al.  Factors affecting nucleosome disassembly by protamines in vitro. Histone hyperacetylation and chromatin structure, time dependence, and the size of the sperm nuclear proteins. , 1987, The Journal of biological chemistry.

[37]  C. Mezquita,et al.  Marked differences in the ability of distinct protamines to disassemble nucleosomal core particles in vitro. , 1986, Biochemistry.

[38]  J. B. Rattner,et al.  Hyperacetylation of histone H4 promotes chromatin decondensation prior to histone replacement by protamines during spermatogenesis in rainbow trout. , 1984, Nucleic acids research.

[39]  S. Grimes,et al.  Hyperacetylation of histone H4 in rat testis spermatids. , 1984, Experimental cell research.

[40]  C. Mezquita,et al.  Histone H4 hyperacetylation and rapid turnover of its acetyl groups in transcriptionally inactive rooster testis spermatids. , 1982, Nucleic acids research.

[41]  R. Balhorn,et al.  DNA and protein content of mouse sperm. Implications regarding sperm chromatin structure. , 1981, Experimental cell research.

[42]  P. Davies,et al.  Acid-soluble nuclear proteins of the testis during spermatogenesis in the winter flounder. Loss of the high mobility group proteins. , 1980, The Journal of biological chemistry.