A non-canonical GLTSCR1L-containing BAF complex mediates H3K27ac-dependent enhancer activities
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA497106 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8065050.fastq.gz | Fastqsanger.gz | |||
| SRR8065060.fastq.gz | Fastqsanger.gz | |||
| SRR8065051.fastq.gz | Fastqsanger.gz | |||
| SRR8065061.fastq.gz | Fastqsanger.gz | |||
| SRR8065052.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:H3K27ac is known to associate with regulatory active enhancers, but it’s exact role in enhancer function remains elusive. Using mass spectrometry-based interaction proteomics, we identified the Super Elongation Complex (SEC) and GBAF, a non-canonical GLTSCR1L- and BRD9-containing SWI/SNF chromatin remodeling complex, to be major interactors of H3K27ac. Our interaction proteomics analysis refined the composition of GBAF by adding BCL7A/B/C as a new subunit. We further characterized the conserved GLTSCR1/1L-contained “GiBAF”-domain, which we found to be responsible for GBAF complex formation and nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and BRD9 to be H3K27ac dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in a genome-wide downregulation of enhancer transcription. Our results indicate that GBAF is an enhancer-associated chromatin remodeller important for the correct transcriptional and regulatory activity of enhancers.
2018-10-17 | GSE121351 | GEO
Project description:The mammalian BRG1-associated factors (BAF) complex is a multi-subunit chromatin remodeling complex that is an important component of the embryonic stem cell (ESC) transcriptional regulatory network. However, the role of individual subunits in BAF complex targeting and function needs to be elucidated. Here, we find that the Bromodomain containing protein 9 (BRD9) defines a smaller, non-canonical BAF complex in mouse ESCs that is distinct from the canonical embryonic stem cell BAF (esBAF) and the polybromo-associated BAF (PBAF) complexes. This BRD9-containing BAF complex, or BBAF complex, uniquely incorporates the BRD4-interacting chromatin remodeling associated protein-like (BICRAL) or its paralog BICRA and lacks several esBAF subunits including BAF47, ARID1A and BAF57. We demonstrate that BBAF and esBAF complexes are targeted to different features of the genome and are co-bound with different sets of pluripotency transcription factors. Specifically, BBAF complexes co-localize with key regulators of naïve pluripotency, KLF4 and Sp5, on the genome. Consistent with this, we provide evidence that BBAF’s specific function is to regulate the transcription of genes involved in the maintenance of naïve pluripotency, including Nanog and Prdm14. Additionally, we show that BRD9 is displaced from chromatin by the selective BRD9 bromodomain inhibitor, I-BRD9, and that this leads to changes in target gene expression. Together, our results provide evidence for the identification of a new BAF complex, and demonstrate functionally specific roles for BAF complex assemblies in maintaining the transcriptional network of pluripotency.
2018-10-18 | PXD010670 | Pride
Project description:The mammalian BRG1-associated factors (BAF) complex is a multi-subunit chromatin remodeling complex that is an important component of the embryonic stem cell (ESC) transcriptional regulatory network. However, the role of individual subunits in BAF complex targeting and function needs to be elucidated. Here, we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1; also known as BICRA) or its paralog GLTSCR1-like (also known as BICRAL) define a smaller, non-canonical BAF complex (GBAF for GLTSCR1/1L-containing BAF complex) in mouse ESCs that is distinct from the canonical embryonic stem cell BAF (esBAF) and the polybromo-associated BAF (PBAF) complexes. GBAF lacks several esBAF subunits, including BAF47, BAF57 and ARID1A. We demonstrate that GBAF and esBAF complexes are targeted to different features of the genome and are co-bound with different sets of pluripotency transcription factors. Specifically, GBAF complexes co-localize with key regulators of naïve pluripotency, KLF4 and Sp5, on the genome. Consistent with this, we provide evidence that GBAF's specific function is to regulate the transcription of genes involved in the maintenance of naïve pluripotency, including Nanog and Prdm14. Additionally, we show that BRD9 is displaced from chromatin by the selective BRD9 bromodomain inhibitor, I-BRD9, and that this leads to changes in target gene expression. The function of the GBAF complex in ESCs is highly correlated with the function of BRD4, consistent with an association between GBAF complexes and BRD4. We find that GBAF complexes are directly recruited to chromatin by BRD4 in a bromodomain-dependent fashion and we identify a set of I-BRD9- and JQ1-sensitive BRD9 binding sites that determine the functional similarity between these epigenetic regulators. Together, our results demonstrate functionally specific roles for BAF complex assemblies in maintaining the transcriptional network of pluripotency, highlighting the biological importance of complex heterogeneity.
2018-10-19 | GSE111264 | GEO
Project description:Spliceosomal disruption of the non-canonical BAF complex in cancer
| PRJNA513262 | ENA
Project description:BRD9-containing non-canonical BAF chromatin remodeling complex acts as a barrier to somatic cell reprogramming
| PRJNA678976 | ENA
Project description:A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naïve pluripotency in mouse embryonic stem cells
| PRJNA436371 | ENA
Project description:Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of mammalian SWI/SNF/BAF complexes in neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here we report that BCL7A is a modulator of the SWI/SNF/BAF complex and stimulates the genome-wide occupancy of the ATPase BRG1. We demonstrate that BCL7A is dispensable for SWI/SNF/BAF complex integrity, whereas it is essential to regulate Notch/Wnt pathway and mitochondrial bioenergetics in differentiating NPCs. Together, our findings uncover the unique mechanistic contribution of BCL7A-containing SWI/SNF/BAF complex in mitochondria-driven NPC commitment, thereby providing a better understanding of the cell-intrinsic transcriptional processes that connect metabolism, neuronal morphogenesis and cognitive flexibility.
2022-10-15 | GSE210759 | GEO
Project description:Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of mammalian SWI/SNF/BAF complexes in neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here we report that BCL7A is a modulator of the SWI/SNF/BAF complex and stimulates the genome-wide occupancy of the ATPase BRG1. We demonstrate that BCL7A is dispensable for SWI/SNF/BAF complex integrity, whereas it is essential to regulate Notch/Wnt pathway and mitochondrial bioenergetics in differentiating NPCs. Together, our findings uncover the unique mechanistic contribution of BCL7A-containing SWI/SNF/BAF complex in mitochondria-driven NPC commitment, thereby providing a better understanding of the cell-intrinsic transcriptional processes that connect metabolism, neuronal morphogenesis and cognitive flexibility.
2022-10-15 | GSE210757 | GEO
Project description:Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of mammalian SWI/SNF/BAF complexes in neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here we report that BCL7A is a modulator of the SWI/SNF/BAF complex and stimulates the genome-wide occupancy of the ATPase BRG1. We demonstrate that BCL7A is dispensable for SWI/SNF/BAF complex integrity, whereas it is essential to regulate Notch/Wnt pathway and mitochondrial bioenergetics in differentiating NPCs. Together, our findings uncover the unique mechanistic contribution of BCL7A-containing SWI/SNF/BAF complex in mitochondria-driven NPC commitment, thereby providing a better understanding of the cell-intrinsic transcriptional processes that connect metabolism, neuronal morphogenesis and cognitive flexibility.
2022-10-15 | GSE210756 | GEO
Project description:Histone acetylation H3K27ac is a well-established chromatin marker for active enhancers and promoters. However, reprogramming dynamics of H3K27ac during maternal-to-zygotic transition (MZT) in mammalian embryos has not been well studied. By profiling the allelic landscape of H3K27ac during mouse MZT, here we show that H3K27ac undergoes three waves of rapid global transitions from oocyte to 2-cell stages. Notably, germinal vesicle (GV) oocyte and zygote are globally hyperacetylated by forming noncanonical broad H3K27ac domains that correlate with broad H3K4me3 and open chromatin. H3K27ac also marks genomic regions primed for activation including ZGA gene promoters, retrotransposons, and active alleles of imprinted genes. Importantly, both CBP/p300 and HDAC activities play important roles in regulating the H3K27ac dynamics and are essential for pre-implantation development. Specifically, CBP/p300 deposits broad H3K27ac domains in zygotes and open condensed chromatin at putative enhancers to ensure proper ZGA. In contrast, HDACs mediate the broad to canonical H3K27ac transition to safeguard ZGA by preventing premature expression of developmental genes and promoting ZGA gene activation. Our study demonstrates that coordinated activities of CBP/p300 and HDACs during mouse MZT are essential for ZGA and mouse pre-implantation development.
2022-08-30 | GSE207222 | GEO