Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evidence for additive and synergistic action of mammalian enhancers during cell fate determination [BRD4-ChIP-seq, H3K4me1-ChIP-seq, TT-seq, RNA-seq]

ABSTRACT: Enhancer activity is known to drive cell differentiation and cell type determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human B-cells to macrophages using enhancer RNA synthesis from accessible, H3K4-monomethylated chromatin regions as a proxy for enhancer activity. Most enhancers cooperate in an additive way to induce transcription of target genes. However, at ~130 loci, enhancers cooperate synergistically, changing activity of target genes exponentially over time. The latter genes are cell type-specific, indicating that enhancer synergy can drive differentiation and cell type determination. Pioneering factor occupancy, DNA accessibility profiling and eRNA synthesis reveal the temporal order of events that lead to enhancer synergy. Our results are consistent with a condensation model for transcription activation of cell type-specific genes that involves simultaneous contacts of multiple enhancers with their target promoter.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149886 | GEO | 2021/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Evidence for additive and synergistic action of mammalian enhancers during cell fate determination [ATAC-seq, CEBPA-ChIP-seq]

Project description:Enhancer activity is known to drive cell differentiation and cell type determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human B-cells to macrophages using enhancer RNA synthesis from accessible, H3K4-monomethylated chromatin regions as a proxy for enhancer activity. Most enhancers cooperate in an additive way to induce transcription of target genes. However, at ~130 loci, enhancers cooperate synergistically, changing activity of target genes exponentially over time. The latter genes are cell type-specific, indicating that enhancer synergy can drive differentiation and cell type determination. Pioneering factor occupancy, DNA accessibility profiling and eRNA synthesis reveal the temporal order of events that lead to enhancer synergy. Our results are consistent with a condensation model for transcription activation of cell type-specific genes that involves simultaneous contacts of multiple enhancers with their target promoter.

2020-06-03 | GSE149885 | GEO

Evidence for additive and synergistic action of mammalian enhancers during cell fate determination

2020-05-06 | GSE131620 | GEO

RNA-seq of GFP positive and negative fractions of zebrafish transgenic cell lines of sea sponge enhancers

Project description:To investigate the activity of sponge enhancers in vertebrates transgenic experiments was performed where sponge enhancers were inserted into zebrafish embryos and stable lines generated abstract: Transcription factors (TFs) bind DNA enhancer sequences to regulate gene transcription in animals. Unlike TFs, the evolution of enhancers has been difficult to trace because of their fast evolution. Here, we take enhancers in the sponge Amphimedon queenslandica and test their activity in zebrafish and mouse. Of the five sponge enhancers assessed, three were located in conserved syntenic gene regions that are unique to animals (Islet–Scaper, Ccne1–Uri, Tdrd3–Diaph3). Despite diverging over 700 million years ago and a dearth of sequence identity, sponge enhancers are able to drive cell type-specific reporter gene expression in vertebrates. Analysis of the type and frequency of TF binding motifs in the sponge Islet enhancer allowed for the identification of homologous enhancers in human and mouse, which show remarkably similar reporter expression patterns to the sponge enhancer. These findings uncover an unexpected deep conservation of enhancers and suggest that enhancers established early in metazoan evolution can remain functional through retention of combinations of transcription factor binding motifs despite substantial sequence divergence.

2019-11-30 | E-MTAB-7846 | biostudies-arrayexpress

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-bound LDB1 Regulates a Corticotrope Promoter Pausing Repression Program [ChIP-seq]

Project description:Substantial evidence supports the hypothesis that enhancers are critical regulators of cell type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of the LIM domain binding protein, LDB1/CLIM2/NLI, interacting with the enhancer binding protein, ASCL1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target target gene promoter genes. While LDB1-dependend activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of MTA2, a component of the NuRD complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type. ChIP assay followed by high throughput sequencing (ChIP-seq)

2015-02-03 | E-GEOD-64483 | biostudies-arrayexpress

Enhancer-bound LDB1 Regulates a Corticotrope Promoter Pausing Repression Program [GRO-seq]

Project description:Substantial evidence supports the hypothesis that enhancers are critical regulators of cell type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of the LIM domain binding protein, LDB1/CLIM2/NLI, interacting with the enhancer binding protein, ASCL1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target target gene promoter genes. While LDB1-dependend activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of MTA2, a component of the NuRD complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type. Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq)

2015-02-03 | E-GEOD-64515 | biostudies-arrayexpress

Enhancers reside in a unique epigenetic environment during early zebrafish development [ChIP-seq & ATAC-seq]

Project description:We describe that during early zebrafish development, DNA methylation has little influence on enhancer activity, and that hypo-methylation is a unique feature of primed enhancers, whereas active enhancers are generally hyper-methylated. Hypo-methylated enhancers (hypo-enhancers) are enriched close to important transcription factors (TFs) that act later in development, are specifically de-methylated before the mid blastula transition (MBT), and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers are functionally active later in development and that they are physically associated with the transcriptional start site (TSS) of target-genes, irrespective of target-gene activity. we analyzed 5 novel ChIP-Seq libraries where we used the following AB (H3K27ac,H3K4me1,H3K4me2 and H3K27ac) and an Atac-Seq library.

2015-11-06 | E-GEOD-74231 | biostudies-arrayexpress

Enhancer-bound LDB1 Regulates a Corticotrope Promoter Pausing Repression Program [GRO-seq]

2015-02-03 | GSE64515 | GEO

Enhancer-bound LDB1 Regulates a Corticotrope Promoter Pausing Repression Program [ChIP-seq]

2015-02-03 | GSE64483 | GEO

Enhancers reside in a unique epigenetic environment during early zebrafish development [4C-seq]

Project description:We describe that during early zebrafish development, DNA methylation has little influence on enhancer activity, and that hypo-methylation is a unique feature of primed enhancers, whereas active enhancers are generally hyper-methylated. Hypo-methylated enhancers (hypo-enhancers) are enriched close to important transcription factors (TFs) that act later in development, are specifically de-methylated before the mid blastula transition (MBT), and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers are functionally active later in development and that they are physically associated with the transcriptional start site (TSS) of target-genes, irrespective of target-gene activity. We performed 6 different 4C-Seq experiment at two different timepoints and in adult brain.

2015-11-06 | E-GEOD-74616 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data