SUMOylation Regulates Super-Enhancers Through Transcription Factor TFAP2C Binding on Chromatin [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA720944 | ENA |
REPOSITORIES: ENA
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Project description:Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing.
2024-04-13 | GSE171804 | GEO
Project description:Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing.
2024-04-13 | GSE171816 | GEO
Project description:SUMOylation Regulates Super-Enhancers Through Transcription Factor TFAP2C Binding on Chromatin
| PRJNA720958 | ENA
Project description:SUMOylation Regulates Super-Enhancers Through Transcription Factor TFAP2C Binding on Chromatin [RNA-seq]
| PRJNA720956 | ENA
Project description:Enhancers are fundamental to gene regulation. Post-translational modifications by the small ubiquitin-like modifiers (SUMO) modify chromatin regulation enzymes, including histone acetylases and deacetylases. However, it remains unclear whether SUMOylation regulates enhancer marks, acetylation at the 27th lysine residue of the histone H3 protein (H3K27Ac). We hypothesize that SUMOylation regulates H3K27Ac. To test this hypothesis, we performed genome-wide ChIP-seq analyses. We discovered that knockdown (KD) of the SUMO activating enzyme catalytic subunit UBA2 reduced H3K27Ac at most enhancers. Bioinformatic analysis revealed that TFAP2C-binding sites are enriched in enhancers whose H3K27Ac was reduced by UBA2 KD. ChIP-seq analysis in combination with molecular biological methods showed that TFAP2C binding to enhancers increased upon UBA2 KD or inhibition of SUMOylation by a small molecule SUMOylation inhibitor. However, this is not due to the SUMOylation of TFAP2C itself. Proteomics analysis of TFAP2C interactome on the chromatin identified histone deacetylation (HDAC) machinery. TFAP2C KD reduced HDAC binding to chromatin and increased H3K27Ac marks at enhancer regions, suggesting that TFAP2C is involved in recruiting HDAC. Taken together, our findings provide important insights into regulation of enhancer marks by SUMOylation.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Here we have used a combination of advanced proteomics and genomics approaches to investigate the extent and mechanisms of transcription factor cross-talk at genomic hotspots. We identify ~12,000 transcription factor hotspots in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate for the first time that hotspots are highly enriched in large super-enhancer regions and that these drive the early adipogenic reprogramming of gene expression. Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers constitute important regulatory hubs integrating external stimuli on chromatin. Genome-wide profiling of transcription factor and co-factor binding, epigenomic marks, and gene expression in 3T3-L1 pre-adipocytes.
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Project description:Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that control and define cell identity. Improved understanding of the roles super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators and core transcription apparatus that occupy super-enhancers in embryonic stem cells (ESCs) and evidence that super-enhancers are highly transcribed. We then use epigenomic data to produce a catalogue of super-enhancers in a broad range of human cell types. These super-enhancer domains are associated with genes encoding master transcription factors and other components that play important roles in the biology of these cells. Interestingly, sequence variation associated with a broad spectrum of diseases is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes that play important roles in tumor pathogenesis. We discuss these insights and their implications for future study of human health and disease. ChIP-Seq for transcription factors in mouse embryonic stem cells and H3K27ac in Jurkat T-ALL cell line RNA-Seq for mouse embryonic stem cells
2013-10-23 | E-GEOD-51522 | biostudies-arrayexpress
Project description:Using GRO-Seq, we find extensive regulation of enhancer RNAs (eRNA) within super-enhancers in response to lipopolysaccharide treatment in macrophages. Both activation and repression of gene expression are associated with super-enhancers and eRNA transcription dynamics. Co-treatment of LPS and the anti-inflammatory drug dexamethasone targeted specific super-enhancers by attenuating their eRNA expression, leading to reduced expression of key inflammatory genes. We propose that super-enhancers function as molecular rheostats integrating the binding profiles of key regulators to produce dynamic profiles of gene expression. Nascent transcriptome (GRO-Seq) analysis over a time course (0, 20, 60, 180 min) of Lipopolisaccharide and Dexamethasone signaling in mouse bone marrow-derived macrophages.
2014-12-25 | E-GEOD-60857 | biostudies-arrayexpress
Project description:Naive and primed pluripotent human embryonic stem cells bear transcriptional similarity to pre- and post-implantation epiblast and thus constitute a developmental model for understanding the pluripotent stages in human embryo development. To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATAC-seq and found enrichment of the activator protein-2 (AP2) transcription factor binding motif at naive-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naive reversion and becomes widespread at naive-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naive-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naive human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse.
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