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Series GSE135340 Query DataSets for GSE135340
Status Public on Jun 23, 2020
Title Enhancer RNA mediate estrogen-induced transcriptional repression by recruiting ERa and its cofactor to selective enhancers [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Estrogen receptor alpha (ERα) signaling mainly occupies on distal enhancers within genome and plays an essential role in ERα-positive breast cancer. ERα usually requires co-factors to regulate the enhancer activity. By analysis of genome-wide nascent transcript profiling in breast cancer cells, we identified a special group of eRNAs that are functionally important for estrogen-induced transcriptional repression. In addition to stabilizing promoter-enhancer looping structure, these eRNAs recruit ERα to particular enhancers of target genes, facilitate the hierarchical formation of a functional transcriptional complex, and cause gene silencing. Interestingly, we found that ERα directly binds to eRNAs and its DNA-binding domain mediates the interaction with RNA molecules. Our ChIP-seq data in MCF-7 cells indicating that ERαwas not able to bind to E2-activated enhancers, which is consistent with the DNA-binding function reported before; moreover the DBD-truncated ERα was not able to bind to E2-repressed enhancers as well, which further supports our hypothesis that eRNA from E2-repressed enhancers help to recruit ERα to specific enhancers through the interaction with DBD domain. Substitution of ERα-DDBD showed a global effect on both induction and repression of ERα target genes as examined by RNA-seq. Further, these eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses transcription of target genes. Our work demonstrated that eRNAs, as a distinctive class of cis-acting molecules besides chromatin regulatory elements, play an important role in modulating and refining locus-specific transcriptional program.
Overall design For MCF7 cells with different ER truncations, MCF7 cells were first infected with lentivirus-based ER truncations, and then transiently infected shER targeting 3'UTR to knock down endogenous ER. Cells were kept in hormone stripped condition for at least three days before treating with 100 nM estradiol or corresponding condition of ethanol for 30 min.ER_pbox/WT ChIP was done in full medium condition.
Chromatin Immunoprecipitation (ChIP) assay followed by high throughput sequencing (ChIP-seq)
Contributor(s) Zhao Z, Mei Y, Kexin X
Citation(s) 32579929
Submission date Aug 03, 2019
Last update date Sep 22, 2020
Contact name Kexin Xu
Organization name UT Health Science Center at San Antonio
Department Molecular Medicine
Street address 7703 Floyd Curl, MC 8257
City San Antonio
State/province Texas
ZIP/Postal code 78229
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (12)
GSM4006670 MCF7, dAF2_ER_E2 (ChIP-Seq)
GSM4006671 MCF7, dAF2_ER_Veh (ChIP-Seq)
GSM4006672 MCF7, dDBD_ER_E2 (ChIP-Seq)
This SubSeries is part of SuperSeries:
GSE135341 Enhancer RNAs mediate estrogen-induced decommissioning of selective enhancers by recruiting ER and its cofactor
BioProject PRJNA558467

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE135340_RAW.tar 2.0 Gb (http)(custom) TAR (of BW)
Raw data are available in SRA
Processed data provided as supplementary file

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