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| Status |
Public on May 15, 2011 |
| Title |
Reprogramming Transcriptional Responses through Functionally-Distinct Classes of Enhancers in Prostate Cancer Cells [ChIP-Seq, Gro-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression.
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| Overall design |
ChIP-Seq, Gro-Seq, and gene expression profiling was performed in LNCaP cells with hormone treatment and siRNA against FoxA1
ChIP-Seq and Gro-Seq data presented here. Supplementary file GroSeq.denovo.transcripts.hg18.bed represents analysis using GSM686948-GSM686950.
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| Contributor(s) |
Kaikkonen MU, Ohgi KH, Glass CK, Rosenfeld MG |
| Citation(s) |
21572438 |
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| Submission date |
Mar 08, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Christopher Benner |
| E-mail(s) |
cbenner@ucsd.edu
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| Organization name |
University of California, San Diego (UCSD)
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| Department |
Medicine
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| Street address |
9500 Gilman Dr. MC 0640
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| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093-0640 |
| Country |
USA |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (30)
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| This SubSeries is part of SuperSeries: |
| GSE27824 |
Reprogramming Transcriptional Responses through Functionally-Distinct Classes of Enhancers in Prostate Cancer Cells |
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| Relations |
| SRA |
SRP005967 |
| BioProject |
PRJNA141903 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27823_GroSeq.denovo.transcripts.hg18.bed.gz |
476.6 Kb |
(ftp)(http) |
BED |
| GSE27823_RAW.tar |
6.3 Gb |
(http)(custom) |
TAR (of BED, BEDGRAPH, FA) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
| Raw data are available in SRA |
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