Molecular architecture of transcription factor hotspots in early adipogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57415 | GEO | 2014/05/08
SECONDARY ACCESSION(S): PRJNA246418
REPOSITORIES: GEO
Similar Datasets
Project description:Here, we have used digital genomic footprinting to precisely define protein localization for several adipogenic transcription factors at a genome-wide level. In combination with ChIP-seq data, these analyses reveal novel molecular insight into the organization of transcription factors at hotpot regions, which provides a new framework for understanding transcription factor cooperativity on chromatin. Digital genomic footprinting and gene expression in 3T3-L1 pre-adipocytes by high throughput sequencing.
2014-05-08 | E-GEOD-57415 | biostudies-arrayexpress
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.
2014-04-17 | E-GEOD-56872 | biostudies-arrayexpress
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.
2014-04-17 | GSE56872 | GEO
Project description:Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPbeta and -delta) to transcription factor 'hotspots'. Our results demonstrate that C/EBPbeta marks a large number of these transcription factor 'hotspots' prior to induction of differentiation and chromatin remodeling and is required for their establishment. Furthermore, a subset of early remodeled C/EBP binding sites persists throughout differentiation and is later occupied by PPAR gamma , indicating that early C/EBP family members, in addition to their well established role in activation of PPAR gamma transcription, may act as pioneering factors for PPAR gamma binding. DNase I hypersensitive chromatin regions and transcription factor binding sites were identified at various time points of 3T3-L1 differentiation using DHS-seq and ChIP-seq, respectively.
2011-03-22 | E-GEOD-27826 | biostudies-arrayexpress
Project description:Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPbeta and -delta) to transcription factor 'hotspots'. Our results demonstrate that C/EBPbeta marks a large number of these transcription factor 'hotspots' prior to induction of differentiation and chromatin remodeling and is required for their establishment. Furthermore, a subset of early remodeled C/EBP binding sites persists throughout differentiation and is later occupied by PPAR gamma , indicating that early C/EBP family members, in addition to their well established role in activation of PPAR gamma transcription, may act as pioneering factors for PPAR gamma binding.
2011-03-22 | GSE27826 | GEO
Project description:Transcription factors have recently been shown to colocalize in hotspot regions of the genome, which are further clustered into super-enhancers. However, the detailed molecular organization of transcription factors at hotspot regions is poorly defined. Here, we have used digital genomic footprinting to precisely define factor localization at a genome-wide level during the early phase of 3T3-L1 adipocyte differentiation, which allows us to obtain detailed molecular insight into how transcription factors target hotspots. We demonstrate the formation of ATF-C/EBP heterodimers at a composite motif on chromatin, and we suggest that this may be a general mechanism for integrating external signals on chromatin. Furthermore, we find evidence of extensive recruitment of transcription factors to hotspots through alternative mechanisms not involving their known motifs and demonstrate that these alternative binding events are functionally important for hotspot formation and activity. Taken together, these findings provide a framework for understanding transcription factor cooperativity in hotspots.
| S-EPMC6360525 | biostudies-literature
Project description:Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 pre-adipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBP(CAAT enhancer binding protein ) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBP.
2017-12-06 | GSE100056 | GEO
Project description:Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 pre-adipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBPß(CAAT enhancer binding protein ß) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBPß.
2017-12-06 | GSE100055 | GEO
Project description:The three dimensional folding of mammalian genomes is cell-type specific and hard to convert suggesting that it is an important layer of gene regulation. Analysis of genome-wide chromosomal associations revealed adipogenesis-specific spatial clustering of adipogenic genes in 3T3-L1 cells. High temporal resolution analysis revealed that the adipogenic "hub", sampled by pparg and Lpin1, undergoes orchestrated reorganization along adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets, points that among all transcription factors tested, RXR is central in genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation the adipogenic hub is shifted to H3K27me3 repressive environment in conjunction with attenuation of gene transcription. Together, we propose stage-specific hierarchy among the orchestra of transcription factors contributing to the establishment of the adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning to H3K27me3 environment in the end of the differentiation may contribute to stabilize gene expression levels and diminish the developmental plasticity of the specialize cell.
2017-07-31 | GSE92475 | GEO
Project description:Here we show through genome-wide binding studies that transcription factor 7-like 1 (TCF7L1) represses structure-related genes during adipogenesis. Intriguingly, TCF7L1 is induced in a cell contact-dependent manner by confluency in preadipocytes and is required for adipocyte differentiation by repressing transcription of cell structure genes. TCF7L1 is also sufficient to bestow adipogenic potential upon non-adipogenic cells. These results implicate TCF7L1 as a novel adipogenic competency factor that uniquely determines adipogenic fate through cell structure organization required for adipocyte gene activation. Examination of TCF7L1 binding in preadipocytes treated for 24 hours with adipogenic stimuli.
2011-09-02 | E-GEOD-31867 | biostudies-arrayexpress