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| Status |
Public on May 02, 2018 |
| Title |
Cooptation of tandem DNA repeats for the control of epithelial-to-mesenchymal transition [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
During normal or pathological epithelial-to-mesenchymal transition, epithelium-specific gene expression is shut down, with the DNA-binding factor ZEB1 acting as a master suppressor of epithelial identity. Here, we show that ZEB1 occupies primate-specific tandem repeats (TRs) harboring dozens of copies of its DNA-binding motif and located within genomic loci relevant for epithelial identity. Deletion of one such repeat in a quasi-mesenchymal human cancer cell line induced the reacquisition of epithelial features and phenocopied the effects of ZEB1 gene deletion. Since ZEB1 binds clustered motifs in a non-cooperative manner, changes in its nuclear concentration enable graded adjustments of TR occupancy, thus fine-tuning repression level. In addition, high motif density in TRs allows ZEB1 binding (and shutdown of epithelial programs) despite differences in chromatin organization and accessibility among epithelial cell types.
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| Overall design |
Chromatin from human pancreatic ductal adenocarcinoma cell line and human colon carcinoma cell line was immunoprecipitated with anti- ZEB1 or anti-CTCF antibodies and subjected to multiparallel sequencing. Experiments were carried out in unmodified cells (MiaPaCa2 and RKO) and genome edited clonal MiaPaCa2 cells (MiaPaCa2.delta-Repeats and the respective control MiaPaCa2.WT).
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| Contributor(s) |
Balestrieri C, Natoli G |
| Citation(s) |
29706544 |
| |
| Submission date |
Oct 14, 2016 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Chiara Balestrieri |
| E-mail(s) |
balestrieri.c@gmail.com
|
| Organization name |
IRCCS San Raffaele Scientific Institute
|
| Department |
Center for Omics Sciences
|
| Street address |
Via Olgettina 58
|
| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE88738 |
Cooptation of tandem DNA repeats for the control of epithelial-to-mesenchymal transition. |
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| Relations |
| BioProject |
PRJNA348428 |
| SRA |
SRP091543 |
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