Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ligand dependent gene regulation by transient ERa clustered enhancers

ABSTRACT: Unliganded Estrogen receptor alpha (ERa) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERa binds to several EREs relatively proximal to the pre-marked, or persistent, ERa-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERa-bound sites, forming Ligand Dependent ERa Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERa condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERa. Our results establish a direct link between ERa condensates, ERa enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136302 | GEO | 2019/11/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ligand dependent gene regulation by transient ERa clustered enhancers

Project description:Ligand dependent gene regulation by transient ERa clustered enhancers

| PRJNA562143 | ENA

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

2013-06-04 | GSE45822 | GEO

An eRNA Transcription Checkpoint For Diverse Signal-dependent Enhancer Activation Programs

Project description:While many or most signal and ligand-dependent pathways function by directing binding of specific transcription factors to large cohorts of regulatory enhancers, the possible “universal” strategies underling activation of these lorge enhancer programs by diverse signals remains poorly understood. Here, we report that ligands, exemplified by estrogen-17-b (E2), cause the recruitment of DNA-PKcs-phosphorylated KAP1 to estrogen receptor a (ERa)-bound enhancers, inhibiting its E3 SUMO ligase activity for the CDK9 subunit of P-TEFb, which permits formation of active P-TEFb required for eRNA elongation overcoming this checkpoint and permitting enhancer activation. We find that most, or all, signal and ligand enhancer activation programs similarly require the loss of SUMOligase function by phoshorylation of KAP1 to prevent Pol II pausing at regulated enhancers. This is based on activation of P-TEFb consequent to deSUMOylation of CDK9, permitting eRNA synthesis. Overcoming this checkpoint appears to be a widely, if not universally, used strategy for signal-dependent enhancer activation because similar events occur on AR and NF-kB-regulated enhancers and even following depolarization acutely-activated neuronal enhancers. This study reveals an unexpected strategy required to overcome a checkpoint common to most or all signal/ligand-regulated enhancers critical to activate broad programs of biologically-important regulatory enhancers that implement the instructions of the endocrine system.

2024-09-17 | GSE240601 | GEO

An eRNA Transcription Checkpoint For Diverse Signal-dependent Enhancer Activation Programs

2024-09-17 | GSE240599 | GEO

An eRNA Transcription Checkpoint For Diverse Signal-dependent Enhancer Activation Programs

2024-09-17 | GSE240598 | GEO

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

Project description:The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNA (ncRNA) transcripts in mammalian cells, bidirectional ncRNAs referred to as eRNAs are present on enhancers. However, it has remained unclear whether these eRNAs are functional, or merely a reflection of enhancer activation. Here, we report that 17 ?-estradiol (E2)-bound estrogen receptor alpha (ER?) on enhancers causes a global increase in eRNA transcription on enhancers adjacent to E2 upregulated coding genes. These induced eRNAs, as functional transcripts, appear to exert important roles for the observed ligand-dependent induction of target coding genes, causing an increased strength of specific enhancer:promoter looping initiated by ER? binding. Cohesin, present on many ER?-regulated enhancers even prior to ligand treatment, apparently contributes to E2-dependent gene activation by stabilizing E2/ER?/eRNA-induced enhancer:promoter looping. Our data indicate that eRNAs are likely to exert important functions in many regulated programs of gene transcription. The ChIP-seqs in this study measure the binding landscape of master transcription regulator of estrogen signaling - ER?, together with common histone marks including H3K27ac and H3K4me1 in MCF7 cells. These data serve as the basis to understand the enhancer map and subsequent analysis of eRNA expression using GRO-seq. The GRO-seq measures the trancription of nascent RNAs in the genome. From MCF7 cells treated with veichle or estrodial, we could identify estrogen-regulated eRNAs and subsequently could study their functions.

2013-06-04 | E-GEOD-45822 | biostudies-arrayexpress

ER alpha rapid signaling is required for estrogen induced proliferation and migration of vascular endothelial cells

Project description:Estrogen receptor alpha (ERa) is required for the protective effects of 17-beta-estradiol (E2, the active, endogenous form of estrogen) after vascular injury or in atherosclerosis. E2-bound ERa can function as a transcription factor which binds directly to chromatin (the genomic pathway). Some ERa is also associated with the plasma membrane and, when bound by E2, activates cellular kinases, including PI3K, Akt and ERK (the rapid signaling pathway). Rapid signaling is mediated by interaction between ERa and the adaptor molecule striatin. Here we identify a triple point mutation (AA 231,233 & 234 KRR->AAA) of full length ERa that blocks its association with striatin and eliminates its ability to perform rapid signaling (without affecting its ability to perform genomic signaling). We have created stably-transfected human vascular endothelial cell lines expressing either WT ERa (WT ECs) or KRR mutant ERa (KRR ECs), and use these cells to show that rapid signaling through ERa is required for the proper regulation of most E2-regulated genes (the data presented in this record), and also for the ability of E2 to stimulate EC migration and proliferation and to inhibit inflammatory monocyte adhesion to ECs.

2016-03-22 | GSE72180 | GEO

ER alpha rapid signaling is required for estrogen induced proliferation and migration of vascular endothelial cells

2016-03-22 | E-GEOD-72180 | biostudies-arrayexpress

Estrogen induces dynamic ERa and RING1B recruitment to control gene and enhancer activities in luminal breast cancer

Project description:We have previously shown that RING1B, a core Polycomb Repressive Complex 1 subunit, is amplified in 22% of breast cancer patients. In ER+ breast cancer, RING1B functionally interacts and co-localizes with ERa at enhancers and actively transcibed genes to modulate oncogenic transcriptional programs. However, the molecular mechanisms underlying this interaction is unclear. Here we demonstrate that in ER+ breast cancer cells, prolonged estrogen (E2) administration induces fluctuations in transcriptional output and chromatin landscape. RING1B loss impairs full E2-mediated gene expression and chromatin accessibility at genomic loci where key breast cancer transcription factors bind. RING1B mediates E2-induced gene expression and chromatin architectural changes both dependently and independently of its enzymatic activity and nucleosomal binding ability. We found that RING1B is recruited to ER, FOXA1, and GRHL2 co-bound sites in a cyclic manner during E2 administration and regulates E2-induced enhancers and ER recruitment. Finally, we characterized the spacial organization pattern between ER, FOXA1, GRHL2, and RING1B on the chromatin at single-nucleotide resolution genome-wide.

2020-06-08 | GSE137579 | GEO

Endothelial ER-alpha Promotes Glucose Tolerance by Enhancing Endothelial Insulin Transport to Skeletal Muscle

Project description:Human aortic endothelial cells were treated with vehicle or estradiol. Immunoprecipitation was then performed with anti-estrogen receptor alpha antibody or mock IgG, and liquid chromatography/tandem mass spectrometry was done. 996859: Mock-IgG-Veh#1; 996860: Mock-IgG-E2#1; 996861: ERa-Veh#1; 996862: ERa-E2#1; 996863: Mock-IgG-Veh#2; 996864: Mock-IgG-E2#2; 996865: ERa-Veh#2; 996866: ERa-E2#2; 996867: Mock-IgG-Veh#3; 996868: Mock-IgG-E2#3; 996869: ERa-Veh#3; 996870: ERa-E2#3

2023-01-19 | MSV000091095 | MassIVE

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