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Developmental and housekeeping transcriptional programs display distinct modes of enhancer-enhancer cooperativity in Drosophila

ABSTRACT: Developmental and housekeeping transcriptional programs display distinct modes of enhancer-enhancer cooperativity in Drosophila

PROVIDER: PRJNA1026644 | ENA |

REPOSITORIES: ENA

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Developmental and housekeeping transcriptional programs display distinct modes of enhancer-enhancer cooperativity in Drosophila

Project description:Genomic enhancers are key transcriptional regulators which, upon the binding of sequence-specific transcription factors, can activate their cognate promoter. Although enhancers have been extensively studied in isolation, a substantial number of genes have more than one simultaneously active enhancer, and it remains unclear how these distinct elements cooperate to regulate transcription. In this work, we report that developmental enhancers – that regulate tissue-specific genes – and housekeeping enhancers rely on distinct modes of enhancer-enhancer cooperativity: while developmental enhancers are synergistic, housekeeping enhancers are additive (meaning that their combined activity mirrors the sum of their individual activities). Developmental enhancer synergy is promiscuous in our system and is not associated with specific combinations of transcription factors. However, developmental transcription factors globally contain higher fraction of intrinsically disordered domains, which might support such synergistic interactions.

2024-09-05 | GSE245033 | GEO

Enhancer-core promoter specificity separates developmental and housekeeping regulation

Project description:Gene transcription in animals involves the assembly of the RNA polymerase II complex at core promoters and its cell type-specific activation by genomic enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different types of core promoters might exhibit an intrinsic specificity towards certain types of enhancers. Here, we show that thousands of enhancers in D. melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a marked specificity towards one of two core promoters M-bM-^@M-^S one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor. Enhancers that activate the housekeeping core promoter are functional across the two different cell types, while developmental enhancers exhibit strong cell type specificity. Both enhancer classes differ in their overall genomic distribution, the functions of neighbouring genes,these genesM-bM-^@M-^Y core promoter elements, as well as the associated factors. Our results provide evidence for a sequence-encoded enhancer-core promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome. STARR-seq was performed in S2 and OSC cells using two core promoters each representing housekeeping and developmental transcription programs. Data for housekeeping promoters (hkCP) are presented in this series; Data for developmental core promoters (dCP) samples are presented in GSE40739.

2014-12-10 | E-GEOD-57876 | biostudies-arrayexpress

Enhancer-core promoter specificity separates developmental and housekeeping regulation

Project description:Gene transcription in animals involves the assembly of the RNA polymerase II complex at core promoters and its cell type-specific activation by genomic enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different types of core promoters might exhibit an intrinsic specificity towards certain types of enhancers. Here, we show that thousands of enhancers in D. melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a marked specificity towards one of two core promoters – one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor. Enhancers that activate the housekeeping core promoter are functional across the two different cell types, while developmental enhancers exhibit strong cell type specificity. Both enhancer classes differ in their overall genomic distribution, the functions of neighbouring genes,these genes’ core promoter elements, as well as the associated factors. Our results provide evidence for a sequence-encoded enhancer-core promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.

2014-12-10 | GSE57876 | GEO

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis

| PRJNA765349 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [RNA-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [RNA-seq]

| PRJNA765029 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ATAC-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ATAC-seq]

| PRJNA765025 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ChIP-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ChIP-seq]

| PRJNA765350 | ENA

Large-scale analysis of the integration of enhancer-enhancer signals by promoters

Project description:Genes are often regulated by multiple enhancers. It is poorly understood how the individual enhancer activities are combined to control promoter activity. Anecdotal evidence has shown that enhancers can combine sub-additively, additively, synergistically, or redundantly. However, it is not clear which of these modes are more frequent in mammalian genomes. Here, we systematically tested how pairs of enhancers activate promoters using a three-way combinatorial reporter assay in mouse cells. By assaying about 69,000 enhancer-enhancer-promoter combinations we found that enhancer pairs generally combine near-additively. This behaviour was conserved across seven developmental promoters tested. Surprisingly, these promoters scale the enhancer signals approximately following a power-law, but the exponent of this response varies between promoters. A housekeeping promoter showed an overall different response to enhancer pairs, and a smaller dynamic range. Thus, our data indicate that enhancers mostly act additively, but promoters transform their collective effect non-linearly.

2023-08-10 | GSE240586 | GEO

Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

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

NextPBM - A platform to study cell-specific transcription factor binding and cooperativity [ChIP-Seq]

Project description:We analyzed binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity using nextPBM, and show how PU.1 affinity correlates with enhancer status and the presence of cooperative and collaborative factors (C/EBPa)

2018-12-18 | GSE123872 | GEO

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