A Novel Germ Cell-specific Protein, SHIP1, Forms a Complex with Chromatin Remodeling Activity during Spermatogenesis*
- Eunyoung Choi‡,
- Cecil Han‡,
- Inju Park‡,
- Boyeon Lee‡,
- Sora Jin‡,
- Heejin Choi‡,
- Do Han Kim‡,
- Zee Yong Park‡,
- Edward M. Eddy§ and
- Chunghee Cho‡,1
- ‡Department of Life Science and Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea and the §Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709
- ↵1 To whom correspondence should be addressed. Fax: 82-62-970-2484; E-mail: choch{at}gist.ac.kr.
Abstract
To determine the mechanisms of spermatogenesis, it is essential to identify and characterize germ cell-specific genes. Here we describe a protein encoded by a novel germ cell-specific gene, Mm.290718/ZFP541, identified from the mouse spermatocyte UniGene library. The protein contains specific motifs and domains potentially involved in DNA binding and chromatin reorganization. An antibody against Mm.290718/ZFP541 revealed the existence of the protein in testicular spermatogenic cells (159 kDa) but not testicular and mature sperm. Immunostaining analysis of cells at various stages of spermatogenesis consistently showed that the protein is present in spermatocytes and round spermatids only. Transfection assays and immunofluorescence studies indicate that the protein is localized specifically in the nucleus. Proteomic analyses performed to explore the functional characteristics of Mm.290718/ZFP541 showed that the protein forms a unique complex. Other major components of the complex included histone deacetylase 1 (HDAC1) and heat-shock protein A2. Disappearance of Mm.290718/ZFP541 was highly correlated with hyperacetylation in spermatids during spermatogenesis, and specific domains of the protein were involved in the regulation of interactions and nuclear localization of HDAC1. Furthermore, we found that premature hyperacetylation, induced by an HDAC inhibitor, is associated with an alteration in the integrity of Mm.290718/ZFP541 in spermatogenic cells. Our results collectively suggest that the Mm.290718/ZFP541 complex is implicated in chromatin remodeling during spermatogenesis, and we provide further information on the previously unknown molecular mechanism. Consequently, we re-designate Mm.290718/ZFP541 as “SHIP1” representing spermatogenic cell HDAC-interacting protein 1.
Footnotes
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↵* This work was supported, in whole or in part, by National Institutes of Health Grant ZO1 ES070077 (Project 1, Intramural Research Program, NIEHS). This work was also supported by the Korea Science and Engineering Foundation Grant RO1-2007-000-20116, Korean Systems Biology Research Grant M10503010001-06N0301-00110, and GIST Systems Biology Infrastructure Establishment grant. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received July 22, 2008.
- Revision received October 2, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
