Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nuclear actin structure regulates chromatin accessibility [RNA-seq]

ABSTRACT: Polymerized b-actin may provide a structural basis for chromatin accessibility. Nuclear actin transport into the nucleus can determine mesenchymal stem cell (MSC) differentiative outcomes through regulated control of gene expression. Using MSC, we show that inhibiting Arp2/3 directed secondary actin branching with CK666, which results in decreased nuclear actin structure, significantly alters chromatin access measured with ATAC-seq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which increases nuclear actin structure. Nuclear visualization shows Arp2/3 inhibition is associated with decreased pericentric H3K9me3 marks. CytoD, in contrast, induces relocation of H3K27me3 marks away from the inner membrane. Treatment induced alterations in the chromatin landscape at 24 hours prompts differential gene expression associated with decreased proliferation and increased differentiation. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest change in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE242943 | GEO | 2024/04/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nuclear actin structure regulates chromatin accessibility [ATAC-seq]

Project description:Polymerized B-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure. In addition, nuclear visualization shows Arp2/3 inhibition decreases pericentric H3K9me3 marks. CytoD, alternatively, induces redistribution of H3K27me3 marks centrally. Such alterations in chromatin landscape are consistent with differential gene expression associated with distinctive differentiation patterns. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest increase in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions.

2024-04-12 | GSE242944 | GEO

Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2 [Epidermis ssRNA-Seq]

Project description:Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis.

2017-11-23 | GSE107265 | GEO

Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2 [Keratinocytes ssRNA-Seq]

2017-11-23 | GSE107264 | GEO

Arp2/3 Complex Activity Enables Nuclear YAP for Naïve Pluripotency of Human Embryonic Stem Cells

Project description:Our understanding of transitions of human embryonic stem cells between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of human embryonic stem cells (hESCs) as they transition from primed to naïve pluripotency that includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for the actin ring, uniform cell mechanics within naïve colonies, nuclear translocation of the Hippo pathway effectors YAP and TAZ, and effective transition to naïve pluripotency. RNA-sequencing analysis confirms that Arp2/3 complex activity regulates Hippo signaling in hESCs, and impaired naïve pluripotency with inhibited Arp2/3 complex activity is rescued by expressing a constitutively active, nuclear-localized YAP-S127A. Moreover, expression of YAP-S127A partially restored in actin filament fence with Arp2/3 complex inhibition, suggesting that actin filament remodeling is both upstream and downstream of YAP activity. These new findings on the cell biology of hESCs reveal a mechanism for cytoskeletal dynamics coordinating cell mechanics to regulate gene expression and facilitate transitions between pluripotency states.

2024-09-11 | GSE276968 | GEO

Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification

Project description:Mouse embryonic stem cells (mESCs), a model for differentiation into primed epiblast-like cells (EpiLCs), have revealed transcriptional and epigenetic control of early embryonic development. The control and significance of morphological changes, however, remain less defined. We show marked changes in morphology and actin architectures during differentiation that depend on Arp2/3 complex but not formin activity. Inhibiting Arp2/3 complex activity pharmacologically or genetically does not block exit from naive pluripotency but attenuates increases in EpiLC markers. We find that inhibiting Arp2/3 complex activity delays formative pluripotency and causes globally defective lineage specification as indicated by RNA-sequencing, with significant effects on TBX3-depedendent transcriptional programs. We also identify two previously unreported indicators of mESC differentiation; MRTF and FHL2, which have inverse Arp2/3 complex-dependent nuclear translocation. Our findings on Arp2/3 complex activity in differentiation and the established role of formins in EMT indicate that these two actin nucleators regulate distinct modes of epithelial plasticity

2022-04-01 | GSE175391 | GEO

Structural biochemistry of the 180 kDa Arp8-module of INO80 defines its function during chromatin remodelling

Project description:Nuclear actin (N-actin) and actin-related proteins (Arps) are critical components of several chromatin modulating complexes, including the chromatin remodeler INO80, but their function is largely elusive. Here, we report the crystal structure of the 180 kDa Arp8-module of S. cerevisiae INO80 and establish its role as an extranucleosomal DNA binding element. The actin-fold of Arp8 engages N-actin in a novel “side-to-front” interaction and specifies thereby recruitment of the Arp4-N-actin heterodimer to the segmented, “two plug” scaffold of the helical HSA domain of Ino80. The HSA domain spans a distance over 120 Å and provides a binding platform for extranucleosomal DNA, which is required for nucleosome sliding and genome-wide nucleosome positioning. Together with the recent cryoEM structure of INO80Core-nucleosome complex, our results provide insights into the mechanism by which INO80 senses 40 bp extranucleosomal entry DNA to conduct highly processive chromatin remodelling.

2018-08-14 | GSE113401 | GEO

Distribution of Arp4 in G2/M phase

Project description:The actin-related proteins (ARPs) comprise a conserved protein family. Arp4p is found in large multisubunits of the INO80 and SWR1 chromatin remodeling complexes and in the NuA4 histone acetyltransferase complex. Here we show that arp4 (arp4S23AD159A) temperature-sensitive cells are defective in G2/M phase function. arp4 mutants are sensitive to the microtubule depolymering agent benomyl and arrest at G2/M phase at restrictive temperature. Arp4p is associated with centromeric and telomeric regions throughout cell cycle. Ino80p, Esa1p, and Swr1p, components of the INO80, NuA4, and SWR1 complexes, respectively, also associate with centromeres. The association of many kinetochore components including Cse4p, a component of the centromere nucleosome, Mtw1p, and Ctf3p is partially impaired in arp4 cells, suggesting that the G2/M arrest of arp4 mutant cells is due to a defect in formation of the chromosomal segregation apparatus. Keywords: ChIP-chip â¢ The goal of the experiment Genome-wide localization of Arp4 binding sites in Saccharomyces cerevisiae â¢ Experimental factors Distribution of Arp4 in WT in G2/M phase in the presence of nocodazole (Saccharomyces cerevisiae). â¢ Experimental design ChIP analysis: Hybridization data for ChIP fraction was compared with WCE (whole cell extract) fraction. Chromosome III, IV,V,VI S. cerevisiae: SC3456a520015F, P/N# 520015, affymetrix tiling array were used.

2010-06-11 | E-GEOD-7276 | biostudies-arrayexpress

Distribution of Arp4 in G2/M phase

2007-03-16 | GSE7276 | GEO

T cell receptor-triggered nuclear actin network formation drives CD4 T cell effector functions

Project description:T cell antigen receptor (TCR) signaling triggers selective cytokine expression to drive T cell proliferation and differentiation required for immune defense and surveillance. The nuclear signaling events responsible for specificity in cytokine gene expression upon T cell activation are largely unknown. Here, we uncover formation of a dynamic actin filament network in the nucleus that regulates cytokine expression for effector functions of CD4 T lymphocytes. TCR engagement triggers the rapid and transient formation of a nuclear actin filament network via nuclear Arp2/3 complex, induced by elevated nuclear Ca2+ levels and regulated via N-Wasp and NIK. Specific interference with TCR-induced formation of nuclear actin filaments impairs production of effector cytokines and prevents generation of antigen-specific antibodies, but does not interfere with immune synapse formation and cell proliferation. Ca2+-regulated actin polymerization in the nucleus allows CD4 T cells the rapid conversion of TCR signals into effector functions required for T cell help Identification of nuclear F-actin sensitive genes upon TCR signaling

2018-11-15 | GSE122531 | GEO

Nuclear actin structure regulates chromatin accessibility.

Project description:Nuclear actin structure regulates chromatin accessibility.

| PRJNA1015586 | ENA