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Enhancer Transcripts Mark Active Estrogen Receptor Binding Sites using GRO-seq

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: W. Lee Kraus

PROVIDER: E-GEOD-43836 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Enhancer transcripts mark active estrogen receptor binding sites.

Hah Nasun N Murakami Shino S Nagari Anusha A Danko Charles G CG Kraus W Lee WL

Genome research 20130501 8

We have integrated and analyzed a large number of data sets from a variety of genomic assays using a novel computational pipeline to provide a global view of estrogen receptor 1 (ESR1; a.k.a. ERα) enhancers in MCF-7 human breast cancer cells. Using this approach, we have defined a class of primary transcripts (eRNAs) that are transcribed uni- or bidirectionally from estrogen receptor binding sites (ERBSs) with an average transcription unit length of ∼3-5 kb. The majority are up-regulated by shor ...[more]

PMID: 23636943

Similar Datasets

Enhancer Transcripts Mark Active Estrogen Receptor Binding Sites

Project description:In this study, we used Global Run-On sequencing (GRO-seq), a method that assays the genome-wide location and orientation of all active RNA polymerases. We generated a global profile of active transcription at ERM-NM-1 binding sites in MCF-7 human breast cancer cells in response to short time course of E2 treatment. This method enabled us to detect active transcription at enhancers and define a class of primary transcripts transcribed uni- or bidirectionally from the ERM-NM-1 binding sites. The raw data used in this study is from GSE27463 but sequenced to a greater depth. Using GRO-seq over a time course (0, 10, 40 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.

2013-05-08 | E-GEOD-43835 | biostudies-arrayexpress

Signaling Pathways Deferentially Affect RNA Polymerase II Initiation, Pausing, and Elongation in Human Cells: TNF-alpha dependent signaling in AC16 cells

Project description:We used Global Run-on and Sequencing (GRO-seq) to measure the rate of transcription elongation by RNA polymerase II (Pol II) following gene activation. We observed that Pol II elongation rates can vary as much as 4-fold at different genomic loci and in response to two distinct cellular signaling pathways (i.e., estrogen and TNFM-NM-1). Elongation rates are slowest near the promoter and increase during the first ~15 kb transcribed into the gene body. Gene body elongation rates correlate with the density of Pol II, consequently resulting in systematically higher rates of transcript production at genes with higher Pol II density. By monitoring Pol II dynamics following short inductions, we found that E2 stimulates gene expression by increasing Pol II initiation, whereas TNFM-NM-1 stimulates the release of Pol II from promoter proximal pause sites. Collectively, our results identify previously uncharacterized variation in the rate of Pol II elongation and highlight elongation as an important, variable, and regulated rate limiting step in the transcription cycle. Using GRO-seq over a time course (0, 10, 25, and 40 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.

2013-04-10 | E-GEOD-41323 | biostudies-arrayexpress

Global Analysis of the Immediate Transcriptional Effects of Estrogen Signaling Reveals a Rapid, Extensive, and Transient Response

Project description:We report the immediate effects of estrogen signaling on the transcriptome of breast cancer cells using Global Run-On and sequencing (GRO-seq). We found that estrogen signaling directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein-coding genes, estrogen regulates the distribution and activity of all three RNA polymerases, and virtually every class of non-coding RNA that has been described to date. This data submission covers >95% of mapped reads comprising nearly all transcript classes described. Reads mapping to intergenic and enhancer transcripts were removed from this data submission and will be reported separately (manuscripts in preparation). Bed files are tab-separated text files in which columns represent: chrom, chromStart (5' End of the read), chromEnd (chromStart+1), name (unused always 'n'), score (the number of mismatches), and strand. Note that because of the inclusion of reads mapping to the rRNA chromosome, bed files cannot be uploaded to the UCSC genome browser directly. Instead, use the wiggle files (coming soon!) for this purpose. Using GRO-seq over a time course (0, 10, 40, 160 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.

2011-05-05 | E-GEOD-27463 | biostudies-arrayexpress

Dynamic Reorganization of the Cardiomyocyte Transcriptome in Response to TNFM-NM-1-induced Proinflammatory Signaling [GRO-Seq]

Project description:Inflammation is associated with many cardiovascular pathologies, but the underlying mechanisms remain unclear. To explore this in more detail, we characterized the transcriptome of an immortalized adult human ventricular cardiomyocyte cell line (AC16) in response to tumor necrosis factor (TNFa). Using a combination of genomic approaches, including global nuclear run-on sequencing (GRO-seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-seq), we identified ~30,000 transcribed regions in AC16 cells, which includes a set of RNA polymerases I and III (Pol I and Pol III) transcribed regions revealed in the presence of M-NM-1-amanitin. The set of transcribed regions produces both protein-coding and non-coding RNAs, many of which have not been annotated previously, including enhancer RNAs originating from NF-M-NM-:B binding sites. In addition, we observed that AC16 cells rapidly and dynamically reorganize their transcriptomes in response to TNFa stimulation in an NF-M-NM-:B-dependent manner, switching from a basal state to a proinflammatory state affecting a spectrum of cardiac-associated protein-coding and non-coding genes. Moreover, we observed distinct Pol II dynamics for up- and downregulated genes, with a rapid release of Pol II into productive elongation for TNFa-stimulated genes. Our studies shed new light on the regulation of the cardiomyocyte transcriptome in response to a proinflammatory signal and help to clarify the link between inflammation and cardiomyocyte function at the transcriptional level. Using GRO-seq and ChIP-seq (p65 and RNA Pol II) over a time course of TNFM-NM-1 signaling in AC16 human cardiomyocytes.

2014-02-27 | E-GEOD-51224 | biostudies-arrayexpress

Dynamic Reorganization of the Cardiomyocyte Transcriptome in Response to TNFM-NM-1-induced Proinflammatory Signaling

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-27 | E-GEOD-51225 | biostudies-arrayexpress

Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters

Project description:RNA polymerases are highly regulated molecular machines. We present a method (GRO-seq) that maps the position, amount, and orientation of transcriptionally-engaged RNA polymerases genome-wide. In this method, nuclear run-on RNAs are subjected to large-scale parallel sequencing and mapped to the genome. Here, we show that peaks of promoter-proximal polymerase reside on ~30% of human genes, transcription extends beyond pre-mRNA 3M-bM-^@M-^Y cleavage, and antisense transcription is prevalent. Additionally, most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes, but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription. Two biological replicates of nascent RNA sequencing

2008-12-04 | E-GEOD-13518 | biostudies-arrayexpress

Fcp1 dephosphorylation of the RNA polymerase II C-terminal domain required for efficient transcription of heat shock genes

Project description:RNA polymerase II is decreased on heat shock-induced genes when the CTD phosphatase Fcp1 is knocked down in Drosophila S2 cells. We examined transcriptionally-engaged Pol II genome-wide with GRO-seq to determine if other genes are similarly affected. Two biological replicates of nascent RNA sequencing

2012-06-28 | E-GEOD-38748 | biostudies-arrayexpress

Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription

Project description:Rev-Erba and Rev-Erbb are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm, metabolism, and inflammatory responses. Rev-Erbs function as transcriptional repressors by recruiting NCoR/HDAC3 co-repressor complexes to Rev-Erb response elements in enhancers and promoters of target genes, but the molecular basis for cell-specific programs of repression is not known. Here, we present evidence that in macrophages, Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby mRNAs, implying a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a method that quantifies nascent 5' ends (5'-GRO-Seq), we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for direct roles of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription. Using ChIPseq, GRO-seq, and 5'GRO-seq to determine mechanism of RevErb in transcriptional regulation in macrophages

2013-06-05 | E-GEOD-45914 | biostudies-arrayexpress

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

Antidiabetic Rosiglitazone Remodels the Adipocyte Transcriptome by Redistributing Transcription to PPARg-Driven Enhancers [HTS]

Project description:Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARg, the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We have now addressed this issue by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Upregulated eRNAs occurred almost exclusively at PPARg binding sites, to which rosi treatment recruited the coactivator MED1. By contrast, transcriptional repression by rosi involved a loss of MED1 from eRNA sites devoid of PPARg and enriched for other TFs including AP-1 factors and C/EBPs. Thus, rosi activates and represses transcription by fundamentally different mechanisms that could inform the future development of antidiabetic drugs. 3T3-L1 matuer adipocyte were treated with rosi, and nascent transcripts were measured at various time points using GRO-seq. ChIP-seq experiments for various coactivators, corepressor, and transcription factors also have been done to monitor initial occupancy or change before and after treatment.

2014-05-02 | E-GEOD-56745 | biostudies-arrayexpress

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