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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2015.01.122 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex.
Nucleic Acids Res
December 2024
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, CB2 0AW, UK.
Article Synopsis
- The human silencing hub (HUSH) complex is an epigenetic system that silences retroelements in the genome, primarily through components like TASOR, MPP8, and Periphilin, which work together to facilitate chromatin modification.
- Periphilin is identified as the main RNA-binding component of the HUSH complex, and its N-terminal domain is crucial for both RNA binding and the overall function of HUSH.
- The study demonstrates that Periphilin can exert HUSH-dependent silencing even when artificially tethered to a transcript that normally would not be silenced, highlighting its importance in the complex's mechanism of action.
Structure and Methyl-lysine Binding Selectivity of the HUSH Complex Subunit MPP8.
J Mol Biol
December 2024
Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address:
The Human Silencing Hub (HUSH) guards the genome from the pathogenic effects of retroelement expression. Composed of MPP8, TASOR, and Periphilin-1, HUSH recognizes actively transcribed retrotransposed sequences by the presence of long (>1.5-kb) nascent transcripts without introns.
View Article and Find Full Text PDFInterplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing.
Nat Commun
November 2024
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
The Human Silencing Hub (HuSH) complex silences retrotransposable elements in vertebrates. Here, we identify a second HuSH complex, designated HuSH2, which is centered around TASOR2, a paralog of the core TASOR protein in HuSH. Our findings reveal that HuSH and HuSH2 localize to distinct and non-overlapping genomic loci.
View Article and Find Full Text PDFPurpose: This study investigates the effects of daily consumption of a probiotic ayran drink on gingival inflammation and the development of experimental gingivitis.
Materials And Methods: This randomised, double-blind, placebo-controlled trial involved 54 volunteer students. The participants were randomly assigned to two groups: the control group received regular ayran for 42 days, while the test group received probiotic enriched ayran (including Lactobacillus acidophilus and Bifidobacterium bifidum) for 42 days twice a day.
Genetically encoded epigenetic sensors for visualization of H3K9me3, H3K9ac and H3K4me1 histone modifications in living cells.
Biochem Biophys Res Commun
November 2024
Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, Bolshoi Blvd. 30, Bld. 1, 121205, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia; Pirogov Russian National Research Medical University, Ostrovityanova 1, 117997, Moscow, Russia. Electronic address:
Post-translational modifications of histones play a crucial role in chromatin structure maintenance and epigenetic regulation. The LiveMIEL (Live-cell Microscopic Imaging of Epigenetic Landscape) method represents a promising approach for tracking histone modifications. It involves visualization of epigenetic modifications using genetically encoded fluorescent sensors and further analysis of the obtained intranuclear patterns by multiparametric image analysis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!