ER and RNA PolII ChIP-seq in WT and ER mutant mouse uterus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56501 | GEO | 2014/04/04
SECONDARY ACCESSION(S): PRJNA243539
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-04-04 | E-GEOD-56501 | biostudies-arrayexpress
Project description:ER and RNA PolII ChIP-seq in WT and ER mutant mouse uterus
| PRJNA243539 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-07 | E-GEOD-48341 | biostudies-arrayexpress
Project description:To advance understanding of mechanisms leading to biological and transcriptional endpoints related to estrogen action in the mouse uterus, we have mapped ERα and RNA polymerase II binding sites using chromatin immunoprecipitation (ChIP) followed by sequencing of enriched chromatin fragments (ChIP-seq). In the absence of hormone, 5184 ERα binding sites were apparent in the vehicle treated ovariectomized uterine chromatin, while 17240 were seen one hour after estrogen (E2) treatment, indicating that some sites are occupied by unliganded ERα, and that ERα binding is increased by E2. Approximately 15% of the uterine ERα binding sites were adjacent to (<10 KB) annotated transcription start sites and many sites are found within genes or are found more than 100 KB distal from mapped genes; however, the density (sites per bp) of ERα binding sites is significantly greater adjacent to promoters. An increase in quantity of sites but no significant positional differences were seen between vehicle and E2 treated samples in the overall locations of ERα binding sites either distal from, adjacent to or within genes. Analysis of the PolII data revealed the presence of poised promoter proximal PolII on some highly upregulated genes. Additionally, co-recruitment of PolII and ERα to some distal enhancer regions was observed. A de novo motif analysis of sequences in the ERα bound chromatin confirmed that estrogen response elements (EREs) were significantly enriched. Interestingly, in areas of ERα binding without predicted ERE motifs, homeodomain transcription factor (Hox) binding motifs were significantly enriched. The integration of the ERα and PolII binding sites from our uterine ChIP-seq data with transcriptional responses revealed in our uterine microarrays has the potential to greatly enhance our understanding of mechanisms governing estrogen response in uterine and other estrogen target tissues.
2012-04-09 | GSE36455 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-11-07 | GSE48341 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-15 | E-GEOD-58633 | biostudies-arrayexpress
Project description: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.
2014-04-03 | GSE56466 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-07-01 | E-GEOD-46124 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-08-08 | GSE112443 | GEO
Project description:ChIP-seq from mice with DNA binding mutations in Esr1 (KIKO mouse). Estrogen Receptor M-NM-1 (ERM-NM-1) interacts with DNA, directly, or indirectly via other transcription factors, referred to as M-bM-^@M-^\tetheringM-bM-^@M-^]. Evidence for tethering is based on in vitro studies and a widely used M-bM-^@M-^\KIKOM-bM-^@M-^] 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 KLF4M-bM-^@M-^Ys 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 ERM-NM-1 binding to hormone response elements (HRE), motifs. KIKO binding to HRE motifs was verified using reporter gene and DNA-binding assays. Because the KIKO ERM-NM-1 has HRE DNA-binding activity, we evaluated the M-bM-^@M-^\EAAEM-bM-^@M-^] ERM-NM-1, which has more severe DBD mutations, and demonstrated lack of ERE or HRE reporter gene induction or DNA binding. The EAAE mouse has an ERM-NM-1-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 ERM-NM-1 tethering, as KIKO ERM-NM-1 effectively stimulates transcription using HRE motifs. The EAAE-ERM-NM-1 DBD mutant mouse demonstrates that ERM-NM-1 DNA-binding is crucial for biological and transcriptional processes in reproductive tissues, and that ERM-NM-1-tethering may not contribute to estrogen-responsiveness in vivo. 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
2014-04-03 | E-GEOD-56466 | biostudies-arrayexpress