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

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

doi

10.1016/j.bbrc.2015.01.122

subject

Has Abstract

pub_date

2015-03-13 00:00:00

pages

470-475

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)00169-2

journal_volume

458

pub_type

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