Dataset Information

Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1) in hepatic cell proliferation at mononucleosomal resolution.

ABSTRACT:

Background

Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases.

Methodology/principal findings

Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real time by quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP). It has been found that Gas1 is expressed not only in quiescent liver but also at the cell cycle G(1)/S transition. The latter expression peak had not been previously reported. Two nucleosomes, flanking a nucleosome-free region, are positioned close to the transcription start site. Both nucleosomes slide in going from the active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition of histone epigenetic marks show distinctive features in both active states: H3K9ac and H3K4me2 are characteristic of transcription in G(0) and H4R3me2 in G(1)/S transition. Sequential-ChIP analysis revealed that the "repressing" mark H3K9me2 colocalize with several "activating" marks at nucleosome N-1 when Gas1 is actively transcribed suggesting a greater plasticity of epigenetic marks than proposed until now. The recruitment of chromatin-remodeling or modifying complexes also displayed distinct characteristics in quiescence and the G(1)/S transition.

Conclusions/significance

The finding that Gas1 is transcribed at the G(1)/S transition suggests that the gene may exert a novel function during cell proliferation. Transcription of this gene is modulated by specific "activating" and "repressing" epigenetic marks, and by chromatin remodeling and histone modifying complexes recruitment, at specific nucleosomes in Gas1 promoter.

SUBMITTER: Sacilotto N

PROVIDER: S-EPMC3153484 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1) in hepatic cell proliferation at mononucleosomal resolution.

Sacilotto Natalia N Espert Antonio A Castillo Josefa J Franco Luis L López-Rodas Gerardo G

PloS one 20110809 8

<h4>Background</h4>Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases.<h4>Methodology/principal findings</h4>Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell prolif ...[more]

PMID: 21858068

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Project description:BackgroundN6-methyladenosine (m6A) and DNA 5-methylcytosine (5mC) methylation plays crucial roles in diverse biological processes, including skeletal muscle development and growth. Recent studies unveiled a potential link between these two systems, implicating the potential mechanism of coordinated transcriptional and post-transcriptional regulation in porcine prenatal myogenesis and postnatal skeletal muscle growth.MethodsImmunofluorescence and co-IP assays were carried out between the 5mC writers and m6A writers to investigate the molecular basis underneath. Large-scale in-house transcriptomic data were compiled for applying weighted correlation network analysis (WGCNA) to identify the co-expression patterns of m6A and 5mC regulators and their potential role in pig myogenesis. Whole-genome bisulfite sequencing (WGBS) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed on the skeletal muscle samples from Landrace pigs at four postnatal growth stages (days 30, 60, 120 and 180).ResultsSignificantly correlated expression between 5mC writers and m6A writers and co-occurrence of 5mC and m6A modification were revealed from public datasets of C2C12 myoblasts. The protein-protein interactions between the DNA methylase and the m6A methylase were observed in mouse myoblast cells. Further, by analyzing transcriptome data comprising 81 pig skeletal muscle samples across 27 developmental stages, we identified a 5mC/m6A epigenetic module eigengene and decoded its potential functions in pre- or post-transcriptional regulation in postnatal skeletal muscle development and growth of pigs. Following integrative multi-omics analyses on the WGBS methylome data and MeRIP-seq data for both m6A and gene expression profiles revealed a genome/transcriptome-wide correlated dynamics and co-occurrence of 5mC and m6A modifications as a consequence of 5mC/m6A crosstalk in the postnatal myogenesis progress of pigs. Last, we identified a group of myogenesis-related genes collaboratively regulated by both 5mC and m6A modifications in postnatal skeletal muscle growth in pigs.ConclusionsOur study discloses a potential epigenetic mechanism in skeletal muscle development and provides a novel direction for animal breeding and drug development of related human muscle-related diseases.

Dataset Information

Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1) in hepatic cell proliferation at mononucleosomal resolution.

Background

Methodology/principal findings

Conclusions/significance

Publications

Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1) in hepatic cell proliferation at mononucleosomal resolution.

Similar Datasets

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