LINC00607 is essential to maintain the endothelial phenotype through SWI/SNF chromatin remodeler BRG1
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ABSTRACT:
PROVIDER: PRJNA833119 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18966461_1.fastq.gz | Fastqsanger.gz | |||
| SRR18966461_2.fastq.gz | Fastqsanger.gz | |||
| SRR18966462_1.fastq.gz | Fastqsanger.gz | |||
| SRR18966462_2.fastq.gz | Fastqsanger.gz | |||
| SRR18966463_1.fastq.gz | Fastqsanger.gz |
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Project description:Long non-coding RNAs (lncRNAs) are regulatory RNAs, which by altering gene expression impact on the cellular phenotype and cardiovascular disease development. The pool of endothelial lncRNAs and their vascular function is largely undefined. Deep-endothelial RNA-Seq and FANTOM5 CAGE analysis revealed LINC00607 as a specifically enriched and highly expressed lncRNA in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA Knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout HUVEC also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored the normal function. RNA- and ATAC-Seq of the LINC00607 knockout revealed changes in transcription of endothelial gene sets particularly linked to the endothelial phenotype. This was most likely the consequence of a reduced chromatin accessibility of the ERG binding motif. Mechanistically, LINC00607 interacts with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is a highly expressed endothelial-specific lncRNA important for efficient endothelial gene transcription through sustaining ERG target gene transcription by interaction with the chromatin remodeler BRG1.
2023-01-09 | GSE201824 | GEO
Project description:Tissue-specific transcription factors initiate differentiation toward a specialized cell type by inducing transcription-permissive chromatin modifications at target gene promoters, through the recruitment of the SWI/SNF chromatin-remodeling complex (1, 2). The molecular mechanism that regulates the chromatin re-distribution of SWI/SNF in response to differentiation signals is currently unknown. Here we show that the muscle determination factor MyoD and the SWI/SNF structural sub-unit, BAF60c (SMARCD3), form a complex on the regulatory elements of MyoD-target genes in undifferentiated myoblasts, prior to the activation of gene expression. MyoD-BAF60c complex is devoid of the ATP-dependent enzymatic sub-units Brg1 and Brm, is required for stable MyoD binding to Ebox sequences, and marks the chromatin for signal-dependent recruitment of the SWI/SNF core complex to muscle loci. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38 signalling promotes the incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which is competent to remodel the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model, by which pre-assembled BAF60c-MyoD complex directs the SWI/SNF complex chromatin re-distribution to muscle loci in response to differentiation cues. Differentiation of C2C12 cells individually interfered for BRG1, BAF60B, BAF60C
2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress
Project description:BRG1-SWI/SNF: Human, Cdx: Mouse Genome sequencing
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Project description:Inositol polyphosphate multikinase (IPMK), a key enzyme in the inositol polyphosphate (IP) metabolism, is a pleiotropic signaling factor involved in major biological events, including transcriptional control. In the yeast, IPMK and its IP products promote the activity of the chromatin-remodeling complex SWI/SNF, which plays a critical role in gene expression by regulating chromatin accessibility. However, the direct link between IPMK and chromatin remodelers remains unclear, raising a question on how IPMK contributes to the transcriptional regulation in mammals. By employing unbiased screening approaches and in vivo/in vitro immunoprecipitations, here we demonstrated that mammalian IPMK physically interacts with the SWI/SNF complex by directly binding to SMARCB1, BRG1, and SMARCC1. Furthermore, we identified the specific domains required for the IPMK-SMARCB1 binding. Notably, using the CUT&RUN and ATAC-seq assays, we discovered that IPMK co-localizes with BRG1 and regulates BRG1 localization as well as BRG1-mediated chromatin accessibility in a genome-wide manner in mouse embryonic stem cells. Finally, our mRNA-seq analyses revealed that IPMK and SMARCB1 regulate the expression of a common gene set, validating a functional link between IPMK and the SWI/SNF complex. Together, these findings show that IPMK regulates promoter-targeting of the SWI/SNF complex and thereby contributes to SWI/SNF-meditated chromatin accessibility, transcription, and differentiation.
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Project description:We monitored changes to genomic binding of BRG1 andBRM following BRG1 or BRM loss to understand how disuprtion of one member of the SWI/SNF complex affected remaining forms of the complex present in the cell.
2017-08-22 | GSE102559 | GEO
Project description:We exogenously expressed the SWI/SNF ATPase catalytic subunits BRG1 and BRM in the lacking cell line C33A, and compared the differences with mock transfected cell at gene expression and alternative splicing level.
2022-03-17 | GSE140474 | GEO
Project description:The noncoding RNA Xist recruits silencing factors to the inactive X chromosome (Xi) and facilitates re-organization of Xi structure. Here, we examine the mouse epigenomic landscape of Xi and assess how Xist alters chromatin accessibility. Xist deletion triggers a gain of accessibility of select chromatin regions that is regulated by BRG1, an ATPase subunit of the SWI/SNF chromatin-remodeling complex. In vitro, RNA binding inhibits nucleosome-remodeling and ATPase activities of BRG1, while in cell culture Xist directly interacts with BRG1 and expels BRG1 from the Xi. Xist ablation leads to a selective return of BRG1 in cis, starting from pre-existing BRG1 sites that are free of Xist. BRG1 re-association correlates with cohesin binding and restoration of topologically associated domains (TADs) and results in the formation of de novo Xi 'superloops'. Thus, Xist binding inhibits BRG1's nucleosome-remodeling activity and results in expulsion of the SWI/SNF complex from the Xi.
| S-EPMC6421574 | biostudies-literature
Project description:Mutations in the SWI/SNF chromatin remodeling complex occur in ~20% of cancers. In rhabdoid tumors defined by loss of the SWI/SNF subunit SMARCB1, dysregulation of enhancer-mediated gene expression is pivotal in driving oncogenesis. Enhancer dysregulation in this setting is tied to retention of the SWI/SNF ATPase BRG1—which becomes essential in the absence of SMARCB1—but precisely how BRG1 contributes to this process remains unknown. To characterize how BRG1 participates in chromatin remodeling and gene expression in SMARCB1-deficient cells, we performed a genome-wide characterization of the impact of BRG1 depletion in multiple rhabdoid tumor cell lines. We find that although BRG1-regulated open chromatin sites are distinct at the locus level, the biological characteristics of the loci are very similar, converging on a set of thematically related genes and pointing to involvement of the AP-1 transcription factor. The open chromatin sites regulated by BRG1 colocalize with histone-marked enhancers and intriguingly include almost all super-enhancers, revealing that BRG1 plays a critical role in maintaining super-enhancer function in this setting. These studies can explain the essentiality of BRG1 to rhabdoid tumor cell identity and survival and implicate the involvement of AP-1 as critical downstream effector of pro-tumorigenic transcriptional programs.
2024-02-23 | GSE241874 | GEO
Project description:The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression, however aberrant remodeling and gene expression can result in cancer. The function and localization on chromatin of the SWI/SNF complex depends on the protein makeup of the complex. Here we report the protein-protein interactions of wild-type BRG1 or mutant BRG1 in which the HSA domain has been deleted (BRG1-HSA). We demonstrate the interaction of BRG1 with most SWI/SNF complex members and a failure of a number of these members to interact with BRG1-HSA. These results demonstrate that the HSA domain of BRG1 is a critical interaction platform for the correct formation of SWI/SNF remodeling complexes.
2023-02-15 | PXD029647 | Pride
Project description:The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors. Genetic deletion of either Pax6 or Brg1, the ATPase unit of the SWI/SNF complex, in neural stem cells of the adult mouse subependymal zone results in a fate conversion to distinct glial subtypes most pronounced when neuroblasts leave the neurogenic niche. Consistent with the phenocopy in vivo virtually all genes down-regulated by Brg1 deletion have Pax6-binding motifs. Amongst the few down-stream transcription factors are Sox11, Nfib and Brn4 that crossregulate each other and rescue neurogenesis also in direct reprogramming in the absence of Brg1 (or Pax6). Thus the function of Pax6-SWI/SNF is necessary and sufficient for neuronal fate maintenance and initiates a cross-regulatory effector network required for neuronal fate execution and maintenance to counteract glial differentiation in the adult brain. This identifies a novel role highly specific role of a chromatin-remodelling complex in stabilizing fate decisions in normal and forced neurogenesis. We performed gene expression microarray analysis on tissue derived from the SEZ or from the core region of the olfactory bulb from Brg1 cKO and control mice
2013-08-01 | E-GEOD-39362 | biostudies-arrayexpress