title: Physical interaction between MPP8 and PRC1 complex and its implication for regulation of spermatogenesis.
abstract: 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.
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Kazuhiro
authors: K
authors: Murata
authors: Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Shinya
authors: S
authors: Sato
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Mayumi
authors: M
authors: Haruta
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Takahiro
authors: T
authors: Goshima
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Yoshie
authors: Y
authors: Chiba
authors: Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors: Satoru
authors: S
authors: Takahashi
authors: Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
authors: Jafar
authors: J
authors: Sharif
authors: Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
authors: Haruhiko
authors: H
authors: Koseki
authors: 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.
authors: Makoto
authors: M
authors: Nakanishi
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. Electronic address: midorism@med.nagoya-cu.ac.jp.
authors: Midori
authors: M
authors: Shimada
mesh_terms: D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000032:analysis / Q000378:metabolism*; D060066:Protein Interaction Maps; D011916:Rats, Inbred F344; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis; D015533:Transcriptional Activation
chemical_list: D006657:Histones; C547278:MPHOSPH8 protein, human; C000597607:Mphosph8 protein, rat; D010750:Phosphoproteins; D063150:Polycomb Repressive Complex 1
keywords: Differentiation; Epigenetics; Spermatocyte; Transcription