EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice

Author:

Dong Yixin12,Isono Kyo-ichi12,Ohbo Kazuyuki3,Endo Takaho A.1,Ohara Osamu1,Maekawa Mamiko4,Toyama Yoshiro4,Ito Chizuru4,Toshimori Kiyotaka4,Helin Kristian5,Ogonuki Narumi6,Inoue Kimiko6,Ogura Atsuo6,Yamagata Kazutsune7,Kitabayashi Issay7,Koseki Haruhiko12

Affiliation:

1. RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan

2. CREST, Japan Science and Technology Agency, Yokohama, Japan

3. Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama, Japan

4. Department of Reproductive Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

5. Biotech Research and Innovation Center and Center for Epigenetics, University of Copenhagen, Copenhagen, Denmark

6. RIKEN BioResource Center, Ibaraki, Japan

7. Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan

Abstract

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.

Funder

grants in aid for scientific research A

grant-in-aid for scientific research C

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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