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Series GSE56466 Query DataSets for GSE56466
Status Public on Apr 03, 2014
Title ERa and PolII ChIP seq from KIKO mouse uterus
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary ChIP-seq from mice with DNA binding mutations in Esr1 (KIKO mouse).
Estrogen Receptor α (ERα) interacts with DNA, directly, or indirectly via other transcription factors, referred to as “tethering”. Evidence for tethering is based on in vitro studies and a widely used “KIKO” mouse model containing mutations that prevent direct estrogen response element (ERE) DNA-binding. KIKO mice are infertile, due in part to the inability of estrogen (E2) to induce uterine epithelial proliferation. To elucidate the molecular events that prevent KIKO uterine growth, regulation of the pro-proliferative E2 target gene Klf4, and of Klf15, a progesterone (P4) target gene that opposes KLF4’s pro-proliferative activity, were evaluated. Klf4 induction was impaired in KIKO uteri; however, Klf15 was induced by E2 rather than by P4. Whole uterine ChIP-seq revealed enrichment of KIKO ERα binding to hormone response elements (HRE), motifs. KIKO binding to HRE motifs was verified using reporter gene and DNA-binding assays. Because the KIKO ERα has HRE DNA-binding activity, we evaluated the “EAAE” ERα, which has more severe DBD mutations, and demonstrated lack of ERE or HRE reporter gene induction or DNA binding. The EAAE mouse has an ERα-null like phenotype, with impaired uterine growth and transcriptional activity. Our findings demonstrate that the KIKO mouse model, which has been used by numerous investigators, cannot be used to establish biological functions for ERα tethering, as KIKO ERα effectively stimulates transcription using HRE motifs. The EAAE-ERα DBD mutant mouse demonstrates that ERα DNA-binding is crucial for biological and transcriptional processes in reproductive tissues, and that ERα-tethering may not contribute to estrogen-responsiveness in vivo.
Overall design one sample each, vehicle ER-alpha ChIP seq,1 hour estradiol ER-alpha ChIP seq, vehicle RNA polymerase II ChIP seq,1 hour estradiol RNA polymerase II ChIP seq, input DNA
Contributor(s) Hewitt SC, Li L, Grimm SA, Fargo D, Korach KS
Citation(s) 24713037
Submission date Apr 02, 2014
Last update date May 15, 2019
Contact name Sylvia C Hewitt
Phone 9842874317
Organization name NIEHS
Department RDBL
Lab Pregnancy & Female Reproduction
Street address 111 Alexander Dr
City Research Triangle Park
State/province NC
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (5)
GSM1361945 KIKO V ER alpha ChIP-seq
GSM1361946 KIKO 1h E2 ER alpha ChIP-seq
GSM1361947 KIKO V PolII alpha ChIP-seq
This SubSeries is part of SuperSeries:
GSE56501 ER and RNA PolII ChIP-seq in WT and ER mutant mouse uterus
BioProject PRJNA243382
SRA SRP040816

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Supplementary file Size Download File type/resource
GSE56466_RAW.tar 833.5 Mb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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