Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hi-C sequencing analysis of wild-type, β-actin knockout and β-actin hetereozygous mouse embryonic fibroblasts

ABSTRACT: β-actin is a crucial component of several chromatin remodeling complexes which control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes. While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversable changes in 3D genome architecture. Our findings support a novel role for β-actin levels in shaping the chromatin landscape during development and differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE149986 | GEO | 2021/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ATAC-Seq analysis of Mouse Embryonic Fibroblasts (MEFs) to understand the role of β-actin in regulating chromatin states

Project description:β-actin is a crucial component of several chromatin remodeling complexes which control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes. While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversable changes in 3D genome architecture. Our findings support a novel role for β-actin levels in shaping the chromatin landscape during development and differentiation.

2020-01-01 | GSE133196 | GEO

Genome-wide ChIP-Seq maps of REST distribution in Wild Type (WT) and Actb-/- (KO) Mouse Embryonic Fibroblast

2021-05-01 | GSE161965 | GEO

Genome-wide ChIP-Seq maps of EZH2 distribution between Wild Type (WT), Actb+/- (HET), and Actb-/- (KO) Mouse Embryonic Fibroblast

2021-05-01 | GSE149961 | GEO

ATAC-Seq analysis of beta actin knockout mouse embryonic fibroblasts expressing NLS-tagged beta-actin

Project description:ATAC-Seq analysis of beta actin knockout mouse embryonic fibroblasts expressing NLS-tagged beta-actin to study impact of actin levels on chromatin accessibility

2022-09-19 | GSE213431 | GEO

TFAM loss induces nuclear actin assembly upon mDia2 malonylation to promote liver cancer metastasis

Project description:The mechanisms underlying cancer metastasis remain poorly understood. Here, we report that TFAM deficiency rapidly and stably induced spontaneous lung metastasis in mice with liver cancer. Interestingly, unexpected polymerization of nuclear actin was observed in TFAM-knockdown HCC cells when cytoskeleton was examined. Polymerization of nuclear actin is causally linked to the high-metastatic ability of HCC cells by modulating chromatin accessibility and coordinating the expression of genes associated with extracellular matrix remodeling, angiogenesis, and cell migration. Mechanistically, TFAM deficiency blocked the TCA cycle and increased the intracellular malonyl-CoA levels. Malonylation of mDia2, which drives actin assembly, promotes its nuclear translocation. Importantly, inhibition of malonyl-CoA production or nuclear actin polymerization significantly impeded the spread of HCC cells in mice. Moreover, TFAM was significantly downregulated in metastatic HCC tissues and was associated with overall survival and time to tumor recurrence of HCC patients. Taken together, our study connects mitochondria to the metastasis of human cancer via uncovered mitochondria-to-nucleus retrograde signaling, indicating that TFAM may serve as an effective target to block HCC metastasis.

2022-06-23 | MTBLS4307 | MetaboLights

In beta-actin knockout mouse embryonic fibroblasts epigenetic reprogramming and chromatin modifications lead to rDNA transcription inactivation and defects in cell growth and proliferation

Project description:Actin and nuclear myosin 1 (NM1) are emerging as regulators of transcription and chromatin organization. Using a genome-wide approach we report here that β-actin binds both intergenic and genic regions across the entire mammalian genome, associated with both protein-coding and rRNA genes. Across the rDNA transcription unit the distribution of β-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In β-actin-/- mouse embryonic fibroblasts (MEFs), we found that rRNA synthesis levels are down-regulated concomitantly with drops in Pol I and NM1 occupancies across the rRNA gene. In knock-in experiments, reintroduction of wild-type β-actin but not mutated forms with polymerization defects, rescued rRNA synthesis underscoring the direct role for β-actin in Pol I transcription and the importance of polymerization during the transcription process. The rRNA defects in the β-actin-/-MEFs are accompanied by epigenetic reprogramming that leads to up-regulation of the repressive mark H3K4me1. In addition, a high resolution chromatin accessibility assay showed that the absence of β-actin leads to a more compact chromatin at specific locations, including promoter-proximal enhancer (T0 sequence) and Sal boxes (T1-T10), disturbing binding of the transcription termination factor 1 (TTF1). We propose a novel mechanism where the polymerase-associated β-actin synergizes with NM1 to coordinate the establishment of permissive chromatin with the correct rDNA topology for Pol I transcription enhancement.

2015-10-04 | GSE68686 | GEO

Actin binding proteins expression levels when modifying the actin sequence

Project description:Actin binding proteins expression levels when modifying the actin sequence

| PRJNA782536 | ENA

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

Project description:Insulin expression is restricted to the pancreatic beta cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-beta cells, particularly in the developmentally related glucagon-secreting alpha cells, is an important aim of regenerative medicine. Here, we performed an RNA interference screen in the murine alpha cell line, alphaTC1, to identify silencers of insulin expression. We discovered that knockdown of the splicing factor Smndc1 (Survival Motor Neuron Domain Containing 1) triggered a global repression of alpha cell gene-expression programs in favor of increased beta cell markers. Mechanistically, Smndc1 knockdown upregulated the key beta cell transcription factor Pdx1, by modulating the activities of the BAF and Atrx families of chromatin remodeling complexes. SMNDC1’s repressive role was conserved in human pancreatic islets, its loss triggering enhanced insulin secretion and PDX1 expression. Our study identifies Smndc1 as a key factor connecting splicing and chromatin remodeling to the control of insulin expression in human and mouse islet cells.

2022-07-01 | PXD030363 | Pride

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

2022-07-01 | PXD030361 | Pride

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

2022-07-01 | PXD030362 | Pride