• PMID: 25660450
• Gene Name: MPHOSPH8
• Condition: Regulation of spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Regulation of spermatogenesis, Male infertility

Physical interaction between MPP8 and PRC1 complex and its implication for regulation of spermatogenesis

Murata K, Sato S, Haruta M, Goshima T, Chiba Y, Takahashi S, Sharif J, Koseki H, Nakanishi M, Shimada M.

Epigenetic modifications such as DNA methylation and histone H3 lysine 27 methylation (H3K27me) are repressive marks that silence gene expression. The M phase phosphoprotein (MPP8) associates with proteins involved in both DNA methylation and histone modifications, and therefore, is a potential candidate to mediate crosstalk between repressive epigenetic pathways. Here, by performing immunohistochemical analyses we demonstrate that MPP8 is expressed in the rodent testis, especially in spermatocytes, suggesting a role in spermatogenesis. Interestingly, we found that MPP8 physically interacts with PRC1 (Polycomb Repressive Complex 1) components which are known to possess essential function in testis development by modulating monoubiquitination of Histone H2A (uH2A) and trimethylation of Histone H3 Lysine 27 (H3K27me3) residues. Knockdown analysis of MPP8 in HeLa cells resulted in derepression of a set of genes that are normally expressed in spermatogonia, spermatids and mature sperm, thereby indicating a role for this molecule in silencing testis-related genes in somatic cells. In addition, depletion of MPP8 in murine ES cells specifically induced expression of genes involved in mesoderm differentiation, such as Cdx2 and Brachyury even in the presence of LIF, which implicated that MPP8 might be required to repress differentiation associated genes during early development. Taken together, our results indicate that MPP8 could have a role for silencing genes that are associated with differentiation of the testis and the mesoderm by interacting with epigenetic repressors modules such as the PRC1 complex. CI - Copyright © 2015 Elsevier Inc. All rights reserved. FAU - Murata, Kazuhiro AU - Murata K AD - Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Sato, Shinya AU - Sato S AD - Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Haruta, Mayumi AU - Haruta M AD - Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Goshima, Takahiro AU - Goshima T AD - Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Chiba, Yoshie AU - Chiba Y AD - Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Takahashi, Satoru AU - Takahashi S AD - Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. FAU - Sharif, Jafar AU - Sharif J AD - Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. FAU - Koseki, Haruhiko AU - Koseki H AD - Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. FAU - Nakanishi, Makoto AU - Nakanishi M AD - Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. Electronic address: mkt-naka@med.nagoya-cu.ac.jp.