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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 03, 2011 |
| Title |
Genome-scale epigenetic reprogramming during epithelial to mesenchymal transition |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
Epithelial to mesenchymal transition (EMT) is an extreme example of cell plasticity, important for normal development, injury repair, and malignant progression. Widespread epigenetic reprogramming occurs during stem cell differentiation and malignant transformation, but EMT-related epigenetic reprogramming is poorly understood. Here we investigated epigenetic modifications during TGF-β-mediated EMT. While DNA methylation was unchanged during EMT, we found global reduction of the heterochromatin mark H3-lys9 dimethylation (H3K9Me2), increase of the euchromatin mark H3-lys4 trimethylation (H3K4Me3), and increase of the transcriptional mark H3-lys36 trimethylation (H3K36Me3). These changes were largely dependent on lysine-specific deaminase-1 (LSD1), and LSD1 loss-of-function experiments showed marked effects on EMT-driven cell migration and chemoresistance. Genome-scale mapping revealed that chromatin changes were largely specific to large organized heterochromatin K9-modifications (LOCKs), suggesting that EMT is characterized by reprogramming of specific chromatin domains across the genome.
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| Overall design |
Chromatin immunoprecipitation (ChIP) was performed with antibodies against H3K9Me2 (Abcam, ab1220), H3K36Me3 (ab9050), and H3K4Me3 (ab8580) on native (unfixed) chromatin isolated from fully differentiated mouse AML12 cells (confluent, serum starved for 48hrs) either treated with TGF-β for 36hrs to induce EMT or not treated with TGF-β (0hrs, differentiated AML12 cells). DNA purified from these samples was then either whole-genome amplified (H3K36Me3 and H3K4Me3) and hybridized or directly (H3K9Me2) hybridized to NimbleGen 2.1M economy whole-genome tiling arrays #2 (listed below as array 1) and #3 (listed below as array 2), which cover mouse chromosomes 4-14. For each sample, the immunoprecipitated DNA (IP) and the input (control) DNA were hybridized to the arrays, and the IP is normalized to the input. There are 16 total samples listed below. There are 8 sample for H3K9Me2 (TGF-β and no TGF-β for arrays 1 and 2, done in replicate for a total of 8). There are 4 samples for H3K36Me3 (TGF-β and no TGF-β done on array 1 and array 2). There are 4 total samples for H3K4Me3 (TGF-β and no TGF-β done on array 1 and array 2).
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| Contributor(s) |
McDonald OG, Wu H, Timp W, Doi A, Feinberg AP |
| Citation(s) |
21725293 |
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| Submission date |
Mar 31, 2011 |
| Last update date |
Jun 05, 2012 |
| Contact name |
Andrew Feinberg |
| E-mail(s) |
afeinberg@jhu.edu
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| Organization name |
Johns Hopkins University
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| Department |
Center for Epigenetics and Department of Medicine
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| Street address |
855 N. Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21212 |
| Country |
USA |
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| Platforms (2) |
| GPL7524 |
NimbleGen mouse (mm8) whole genome tiling array 2 of 4 [2007-08-17_MM8_Economy_02] |
| GPL7525 |
NimbleGen mouse (mm8) whole genome tiling array 3 of 4 [2007-08-17_MM8_Economy_03] |
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| Samples (16)
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| GSM700049 |
H3K9me2 36-hour TGFb, array 2 |
| GSM700050 |
H3K9me2 no TGF-b, array 1 replicate |
| GSM700051 |
H3K9me2 no TGF-b, array 2 replicate |
| GSM700052 |
H3K9me2 36-hour TGFb, array 1 replicate |
| GSM700053 |
H3K9me2 36-hour TGFb, array 2 replicate |
| GSM700054 |
H3K36me3 no TGF-b, array 1 |
| GSM700055 |
H3K36me3 no TGF-b, array 2 |
| GSM700056 |
H3K36me3 36-hour TGF-b, array 1 |
| GSM700057 |
H3K36me3 36-hour TGF-b, array 2 |
| GSM700058 |
H3K4me3 no TGF-b, array 1 |
| GSM700059 |
H3K4me3 no TGF-b, array 2 |
| GSM700060 |
H3K4me3 36-hour TGF-b, array 1 |
| GSM700061 |
H3K4me3 36-hour TGF-b, array 2 |
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| This SubSeries is part of SuperSeries: |
| GSE28581 |
Epigenomic reprogramming during epithelial to mesenchymal transition |
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| Relations |
| BioProject |
PRJNA143201 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28291_RAW.tar |
716.2 Mb |
(http)(custom) |
TAR (of XYS) |
| Processed data included within Sample table |
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