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Series GSE9253 Query DataSets for GSE9253
Status Public on Oct 19, 2007
Title Genomic analyses of TF binding, histone acetylation and gene expression reveal classes of E2-regulated promoters
Organism Homo sapiens
Experiment type Expression profiling by array
Summary To explore the global mechanisms of estrogen-regulated transcription, we used chromatin immunoprecipitation coupled with DNA microarrays to determine the localization of RNA polymerase II (Pol II), estrogen receptor alpha (ERalpha), steroid receptor coactivator proteins (SRC), and acetylated histones H3/H4 (AcH) at estrogen-regulated promoters in MCF-7 cells with or without estradiol (E2) treatment. In addition, we correlated factor occupancy with gene expression and the presence of transcription factor binding elements. Using this integrative approach, we defined a set of 58 direct E2 target genes based on E2-regulated Pol II occupancy and classified their promoters based on factor binding, histone modification, and transcriptional output. Many of these direct E2 target genes exhibit interesting modes of regulation and biological activities, some of which may be relevant to the onset and proliferation of breast cancers. Our studies indicate that about one-third of these direct E2 target genes contain promoter-proximal ERalpha-binding sites, which is considerably more than previous estimates. Some of these genes represent possible novel targets for regulation through the ERalpha/AP-1 tethering pathway. Our studies have also revealed several previously uncharacterized global features of E2-regulated gene expression, including strong positive correlations between Pol II occupancy and AcH levels, as well as between the E2-dependent recruitment of ERalpha and SRC at the promoters of E2-stimulated genes. Furthermore, our studies have revealed new mechanistic insights into E2-regulated gene expression, including the absence of SRC binding at E2-repressed genes and the presence of constitutively bound, promoter-proximally paused Pol IIs at some E2-regulated promoters. These mechanistic insights are likely to be relevant for understanding gene regulation by a wide variety of nuclear receptors.
Keywords: MCF7 cells, E2, Estrogen, RNA, ER, RNA Polymerase II, SRC, Acetylated histones, ChIP-chip
Overall design See Materials and Methods in the associated publication for more details
Contributor(s) Kininis M, Chen BS, Diehl AG, Isaacs GD, Zhang T, Siepel AC, Clark AG, Kraus WL
Citation(s) 17515612
Submission date Oct 05, 2007
Last update date Mar 25, 2019
Contact name W. Lee Kraus
Organization name UT Southwestern Medical Center
Street address 5323 Harry Hines Blvd.
City Dallas
State/province TX
ZIP/Postal code 75390-8511
Country USA
Platforms (3)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
GPL6229 Kraus_lab Human custom PCR-based spotted microarray
Samples (24)
GSM234903 MCF7_EtOH_replicate1
GSM234904 MCF7_EtOH_replicate2
GSM234905 MCF7_EtOH_replicate3
BioProject PRJNA102871

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9253_RAW.tar 24.1 Mb (http)(custom) TAR (of CEL, GPR)
Processed data included within Sample table

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