The histone variant macroH2A1 regulates key genes for myogenic cell fusion in a splice-isoform dependent manner
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PROVIDER: PRJNA622946 | ENA |
REPOSITORIES: ENA
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Project description:MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at the present it is not clear how macroH2As affect gene regulation to exert these functions. Here, we have addressed the question of whether the two splice isoforms of macroH2A1 differentially regulate genes in a physiological context. We have focused on myotube formation that is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of myotubes differentiated ex vivo that was indicative of reduced fusion. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype with macroH2A1.1 enhancing and macroH2A1.2 reducing fusion. Transcriptomic analysis allowed us to associate this phenotype with the differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion. In conclusion, we describe for the first time splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel, yet unknown underlying molecular mechanism of gene regulation independent of PARP1.
2020-04-03 | GSE148044 | GEO
Project description:MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at the present it is not clear how macroH2As affect gene regulation to exert these functions. Here, we have addressed the question of whether the two splice isoforms of macroH2A1 differentially regulate genes in a physiological context. We have focused on myotube formation that is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of myotubes differentiated ex vivo that was indicative of reduced fusion. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype with macroH2A1.1 enhancing and macroH2A1.2 reducing fusion. Transcriptomic analysis allowed us to associate this phenotype with the differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion. In conclusion, we describe for the first time splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel, yet unknown underlying molecular mechanism of gene regulation independent of PARP1.
2020-04-03 | GSE147590 | GEO
Project description:The histone variant macroH2A1 regulates key genes for myogenic cell fusion in a splice-isoform dependent manner [RNA-Seq]
| PRJNA615657 | ENA
Project description:The histone variant macroH2A1 regulates key genes for myogenic cell fusion in a splice-isoform dependent manner [ChIP-Seq]
| PRJNA622955 | ENA
Project description:MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at present, it is not clear how macroH2As affect gene regulation to exert these functions. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of murine myotubes differentiated ex vivo. The fusion of myoblasts to myotubes is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have focused on this physiological process, to investigate the functions of the two splice isoforms of macroH2A1. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype, with macroH2A1.1 enhancing, and macroH2A1.2 reducing, fusion. Differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion correlated with these phenotypes. We describe, for the first time, splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel underlying molecular mechanism of gene regulation.
| S-EPMC7290658 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-03 | GSE148045 | GEO
Project description:Epigenetic regulation of DNA repair pathway choice by macroH2A1 splice variants ensures genome stability
2020-06-03 | MSV000085541 | MassIVE
Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1M-bM-^@M-^Ys role in cancer suppression. Two biological replicates of the macroH2A1 ChIP and two corresponding input samples were sequenced
2014-09-15 | E-GEOD-54845 | biostudies-arrayexpress
Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression.
2014-09-15 | GSE54845 | GEO
Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression. Three biological replicates of RNA-seq from cells expressing shRNA directed against macroH2A1 or luciferase as a control
2014-09-15 | E-GEOD-54846 | biostudies-arrayexpress