Cohesin regulates alternative splicing alone or with BRD4
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182960 | GEO | 2022/08/31
REPOSITORIES: GEO
Similar Datasets
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors. WI38 cells have been treated by heatshock and anti BRD4 siRNA and combination.
2016-09-07 | E-GEOD-73471 | biostudies-arrayexpress
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors.
2016-09-07 | GSE73471 | GEO
Project description:Rad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21. The zebrafish Rad21 mutant used for expression analysis was rad21nz171, an allele isolated in a forward genetic screen for regulators of runx1. Experiment Overall Design: RNA from rad21nz171 mutant and wild type zebrafish embryos collected at 24 hours post-fertilization (h.p.f.) and 48 h.p.f. was hybridized to Affymetrix microarrays (Gene Chip zebrafish genome arrays cat. no. 900488). Four pools of 50 embryos for each genotype and time point were used as the RNA source, and RNA from each pool was hybridized independently such that the experiment had four biological replicates.
2009-11-10 | E-GEOD-18795 | biostudies-arrayexpress
Project description:H3K27Ac ChIP-seq in wild type and cohesin-deficient thymocytes Rad21 was deleted in CD4+ CD8+ double positive (DP) thymocytes by crossing a Rad21 floxed allele with a Cd4-driven Cre transgene. DP positive thymocytes were FACS-sorted from control and Rad21-/- littermates, which were then used to perform chromatin immunoprecipitation for histone H3 acetylated on lysine 27 (H3K27Ac).
2015-02-12 | E-GEOD-61428 | biostudies-arrayexpress
Project description:Rad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21. The zebrafish Rad21 mutant used for expression analysis was rad21nz171, an allele isolated in a forward genetic screen for regulators of runx1.
2009-10-30 | GSE18795 | GEO
Project description:We performed RNA-sequencing in c-Kit+ cells that were infected with retroviruses expressing shRNAs for Renilla, Rad21, Smc1a, Smc3 or Stag2. These cells were grown in methylcellulose (M3434) for either one passage (P1) or replated for five passages (P5). RNA-sequencing control (Ren) and cohesin (Rad21, Smc1a, Smc3 and Stag2) knockdown cells.
2015-09-16 | E-GEOD-72368 | biostudies-arrayexpress
Project description:Cohesin, a chromatin-associated protein complex with four core subunits (Smc1a, Smc3, Rad21 and either Stag1 or 2), has a central role in cell proliferation and gene expression in metazoans. Human developmental disorders termed “cohesinopathies” are characterised by germline mutations in cohesin or its regulators that do not entirely eliminate cohesin function. However, it is not clear if mutations in individual cohesin subunits have independent developmental consequences. Using zebrafish rad21 or stag2 mutants to change cohesin complex quantity or composition, we show that these parameters independently influence embryonic tailbud development. Both mutants have altered mesoderm induction, but only homozygous or heterozygous rad21 mutation affects cell cycle gene expression. stag2 mutants have slimmer notochords and reduced Wnt signaling in neuromesodermal progenitors as revealed by single cell RNA-sequencing. Stimulation of Wnt signaling rescues transcription and morphology in stag2, but not rad21 mutants, implying that individual cohesin mutations respond independently to cell signaling. Our results have implications for the understanding and management of cohesinopathies.
2023-11-29 | GSE247246 | GEO
Project description:Cohesin, a chromatin-associated protein complex with four core subunits (Smc1a, Smc3, Rad21 and either Stag1 or 2), has a central role in cell proliferation and gene expression in metazoans. Human developmental disorders termed “cohesinopathies” are characterised by germline mutations in cohesin or its regulators that do not entirely eliminate cohesin function. However, it is not clear if mutations in individual cohesin subunits have independent developmental consequences. Using zebrafish rad21 or stag2 mutants to change cohesin complex quantity or composition, we show that these parameters independently influence embryonic tailbud development. Both mutants have altered mesoderm induction, but only homozygous or heterozygous rad21 mutation affects cell cycle gene expression. stag2 mutants have slimmer notochords and reduced Wnt signaling in neuromesodermal progenitors as revealed by single cell RNA-sequencing. Stimulation of Wnt signaling rescues transcription and morphology in stag2, but not rad21 mutants, implying that individual cohesin mutations respond independently to cell signaling. Our results have implications for the understanding and management of cohesinopathies.
2023-11-29 | GSE248952 | GEO
Project description:In eukaryotes, the nuclear chromatin in the interphase is a hierarchical organization. Previous studies have suggested that cohesin-DNA interactions play important architectural functions for chromatin structure in the interphase. In this study, we applied super-resolution imaging, single-molecule imaging to measure the distribution of cohesin subunits. Hi-C and RNA-seq were used to reveal the 3D genome structures alterations and the relationship with breast cancer upon Rad21 up-regulation. Hi-C experiment showed that the contact frequency of short distance was increased while that of long distance was decreased in the absence of Rad21 up-regulation. Chromatin interactions between A and B compartments increased and compartmentalization strength was reduced significantly upon Rad21 up-regulation. Correspondingly, accumulated contacts were shown at TAD corners and inter-TAD interactions increased. These observations support cohesin loop extrusion model and lead us to propose the unique role of Rad21-loader interaction in cohesin loading and further cohesin extrusion. Moreover, we combined transcriptome changes and chromatin structure alterations upon Rad21 up-regulation and revealed the correlation between Rad21 and breast cancer by affecting chromatin architecture.
2022-05-01 | GSE183186 | GEO
Project description:Identification of cohesin (Rad21) and CTCF binding sites in ~2% of the mouse genome in B3 pre-B cells stably expressing FLAG-tagged Rad21 using anti-FLAG (Sigma F3165) and anti-CTCF (Upstate 07729) antibodies
2008-01-31 | E-TABM-401 | biostudies-arrayexpress