Similar Datasets
Project description:The RNA transcribed from enhancer regions, referred to as eRNA, has been suggested to directly activate transcription by helping to recruit transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find the AT-hook of SWI/SNF alone binds preferentially RNA and as part of the esBAF complexes associates with eRNA transcribed from intronic and intergenic regions. SWI/SNF is globally recruited in cis by eRNA to cell-type specific enhancers at two distinct stages in early mammalian development and not at promoters or enhancers that are shared between the two stages. SWI/SNF recruited by eRNA facilitates recruitment and/or activation of MLL3/4, p300/CBP and Mediator co-activators to stage-specific super-enhancers that in the primed embryonic stage activate cell lineage priming related genes. We find a strong connection between ATP-dependent chromatin remodeling and eRNA in cell identity and super-enhancer activation.
2023-08-25 | GSE207788 | GEO
Project description:The RNA transcribed from enhancer regions, referred to as eRNA, has been suggested to directly activate transcription by helping to recruit transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find the AT-hook of SWI/SNF alone binds preferentially RNA and as part of the esBAF complexes likely associates with eRNA that are transcribed from intronic and intergenic regions. SWI/SNF is globally recruited in cis by eRNA to cell-type specific enhancers at two distinct stages in early mammalian development and not at promoters or enhancers that are shared between the two stages. SWI/SNF recruited by eRNA facilitates recruitment and/or activation of MLL3/4, p300/CBP and Mediator co-activators to stage-specific super-enhancers that in the primed embryonic stage activate cell lineage priming related genes. We find a strong connection between ATP-dependent chromatin remodeling and eRNA in cell identity and super-enhancer activation.
2023-07-10 | GSE236261 | GEO
Project description:The RNA transcribed from enhancer regions, referred to as eRNA, has been suggested to directly activate transcription by helping to recruit transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find the AT-hook of SWI/SNF alone binds preferentially RNA and as part of the esBAF complexes likely associates with eRNA that are transcribed from intronic and intergenic regions. SWI/SNF is globally recruited in cis by eRNA to cell-type specific enhancers at two distinct stages in early mammalian development and not at promoters or enhancers that are shared between the two stages. SWI/SNF recruited by eRNA facilitates recruitment and/or activation of MLL3/4, p300/CBP and Mediator co-activators to stage-specific super-enhancers that in the primed embryonic stage activate cell lineage priming related genes. We find a strong connection between ATP-dependent chromatin remodeling and eRNA in cell identity and super-enhancer activation.
2023-07-10 | GSE236752 | GEO
Project description:Notch signaling plays a key role in many cell fate decisions during development by directing different gene expression programs via the transcription factor CSL, known as Su(H) in Drosophila Which target genes are responsive to Notch signaling is influenced by the chromatin state of enhancers, yet how this is regulated is not fully known. Detecting a specific increase in the histone variant H3.3 in response to Notch signaling, we tested which chromatin remodelers or histone chaperones are required for the changes in enhancer accessibility to Su(H) binding. We show a crucial role for the Brahma SWI/SNF chromatin remodeling complex, including the actin-related BAP55 subunit, in conferring enhancer accessibility and enabling the transcriptional response to Notch activity. The Notch-responsive regions have high levels of nucleosome turnover which depend on the Brahma complex, increase in magnitude with Notch signaling, and primarily involve histone H3.3. Together these results highlight the importance of SWI/SNF-mediated nucleosome turnover in rendering enhancers responsive to Notch.
| S-EPMC6500979 | biostudies-literature
Project description:The variant histone macroH2A helps maintain X inactivation and gene silencing. Previous work implied that nucleosomes containing macroH2A cannot be remodeled by ISWI and SWI/SNF chromatin remodeling enzymes. Using approaches that prevent misassembly of macroH2A nucleosomes, we find that macroH2A nucleosomes are excellent substrates for both enzyme families. Interestingly, SWI/SNF, which is involved in gene activation, preferentially binds H2A nucleosomes over macroH2A nucleosomes, but ACF, an ISWI complex implicated in gene repression, shows no preference. Thus, macroH2A may help regulate the balance between activating and repressive remodeling complexes.
| S-EPMC3428728 | biostudies-literature
Project description:Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations. Here, we review the current landscape of mechanistic insights and emerging therapeutic opportunities for human malignancies driven by mSWI/SNF complex perturbation.
| S-EPMC5777332 | biostudies-literature
Project description:SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared by all subtypes, such as SPRY1, and other lineage-specific super-enhancers, such as SOX2 in brain-derived rhabdoid tumors. Taken together, our findings identify a new chromatin-based epigenetic mechanism underlying the tumor-suppressive activity of SMARCB1.
| S-EPMC5285474 | biostudies-literature
Project description:Heterozygous germline mutations in components of switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes were recently identified in patients with non-syndromic intellectual disability, Coffin-Siris syndrome and Nicolaides-Baraitser syndrome. The common denominator of the phenotype of these patients is severe intellectual disability and speech delay. Somatic and germline mutations in SWI/SNF components were previously implicated in tumor development. This raises the question whether patients with intellectual disability caused by SWI/SNF mutations in the germline are exposed to an increased risk of developing cancer. Here we compare the mutational spectrum of SWI/SNF components in intellectual disability syndromes and cancer, and discuss the implications of the results of this comparison for the patients.
| S-EPMC3499322 | biostudies-literature
Project description:Mammals have partially lost the extensive regenerative capabilities of some vertebrates, possibly as a result of chromatin-remodeling mechanisms that enforce terminal differentiation. Here, we show that deleting the SWI/SNF component Arid1a substantially improves mammalian regeneration. Arid1a expression is suppressed in regenerating tissues, and genetic deletion of Arid1a increases tissue repair following an array of injuries. Arid1a deficiency in the liver increases proliferation, reduces tissue damage and fibrosis, and improves organ function following surgical resection and chemical injuries. Hepatocyte-specific deletion is also sufficient to increase proliferation and regeneration without excessive overgrowth, and global Arid1a disruption potentiates soft tissue healing in the ear. We show that Arid1a loss reprograms chromatin to restrict promoter access by transcription factors such as C/ebpα, which enforces differentiation, and E2F4, which suppresses cell-cycle re-entry. Thus, epigenetic reprogramming mediated by deletion of a single gene improves mammalian regeneration and suggests strategies to promote tissue repair after injury.
| S-EPMC4826298 | biostudies-literature
Project description:Transcriptional activation of yeast INO1 requires SWI/SNF and INO80 for nucleosome disruption at the promoter. However, the cooperative interplay among remodelers and their recruitment dynamics in activation have thus far been vague. Here, we showed, using chromatin immunoprecipitation, that both SWI/SNF and INO80 are present at the promoter and are restricted to the promoter, indicating that they directly participate in localized INO1 chromatin remodeling. Furthermore, both SWI/SNF and INO80 are absent at the INO1 promoter in ino2Delta cells, suggesting that these are activator-dependent remodelers. We have also found that the presence of INO80 is required for SWI/SNF recruitment, indicating that INO80 arrives first at the promoter followed by SWI/SNF. In light of these findings, we proposed a model which describes the order of events in INO1 activation.
| S-EPMC2536487 | biostudies-literature