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| Status |
Public on Apr 29, 2010 |
| Title |
Estrogen-mediated Epigenetic Repression of Large Chromosomal Regions through DNA Looping |
| Organisms |
Homo sapiens; Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by genome tiling array
Expression profiling by array
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| Summary |
The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. To comprehensively characterize the influence of estrogen signaling on LRES, we analyzed transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This ?omics? approach uncovered 11 large repressive zones (range: 0.35~5.98 megabases), including a 14-gene cluster located on 16p11.2. In normal cells, estrogen signaling induced transient formation of multiple DNA loops in the 16p11.2 region by bringing 14 distant loci to focal ESR1-docking sites for coordinate repression. However, the plasticity of this free DNA movement was reduced in breast cancer cells. Together with the acquisition of DNA methylation and repressive chromatin modifications at the 16p11.2 loci, an inflexible DNA scaffold may be a novel determinant used by breast cancer cells to reinforce estrogen-mediated repression.
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| Overall design |
ChIP-seq: E2-preexposed or DMSO-preexposed mammosphere-derived epithelial cells (MDECs); MCF-7 cells with 4hr of DMSO or E2 stimulation.
MeDIP-chip: Methylated DNA from MCF7 cells was immunoprecipitated by the antibody against 5-methyl cytidine. The immunoprecipitated methylated DNA fragments were processed by the NimbleGen Methylation Microarray Service. Methylation analysis was performed on the NimbleGen Two-Array HG18 Promoter Set.
mRNA profiling by array: Four sets of total RNA samples from the mammary gland of each 50-day-old rat with prepubertal exposure of BPA. Each sample set includes one BPA-exposed and one sesame oil-exposed rat RNA.
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| Contributor(s) |
Hsu P, Pereira JS, Lopez R, Russo J, Lamartiniere CA, Yan P, Liu J, Singer GA |
| Citation(s) |
20442245, 21072189 |
| Submission date |
Mar 25, 2010 |
| Last update date |
Aug 19, 2019 |
| Contact name |
Pei-Yin Hsu |
| Organization name |
OSU
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| Street address |
BRT836, 460W 12th Ave
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| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43220 |
| Country |
USA |
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| Platforms (4)
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| GPL4135 |
Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Feature Number version) |
| GPL6325 |
NimbleGen Homo sapiens HG18 promoter 1 of 2 |
| GPL6326 |
NimbleGen Homo sapiens HG18 promoter 2 of 2 |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (12)
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| GSM529977 |
MDEC_E2-preexposed_rep1 [ChIP-seq] |
| GSM529978 |
MDEC_DMSO-preexposed_rep1 [ChIP-seq] |
| GSM529979 |
MDEC_DMSO-preexposed_rep2 [ChIP-seq] |
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| Relations |
| SRA |
SRP002398 |
| BioProject |
PRJNA126731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21068_RAW.tar |
164.5 Mb |
(http)(custom) |
TAR (of GFF, PAIR, TXT, WIG) |
| GSE21068_mRNAprofiling_sig-genes.txt.gz |
4.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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