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| Status |
Public on Apr 09, 2013 |
| Title |
Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tissue-specific differentiation programs become dysregulated during cancer evolution. The transcription factor Nkx2-1 is a master regulator of pulmonary differentiation that is downregulated in poorly differentiated lung adenocarcinoma. Here we use conditional murine genetics to study the fate of lung epithelial cells upon loss of their master cell fate regulator. Nkx2-1 deletion in normal and neoplastic lung causes not only loss of pulmonary identity but also gastric transdifferentiation. Nkx2-1 maintains pulmonary identity by sequestering the Foxa1 transcription factor at lung-specific loci and by inhibiting Foxa1 binding to gastrointestinal targets. Murine Nkx2-1-negative lung tumors mimic the mucinous subtype of human lung adenocarcinoma, which also exhibits gastric transdifferentiation. Nkx2-1-negative lung adenocarcinomas are dependent on the gastrointestinal gene Hnf4a for efficient initiation. Thus, loss of Nkx2-1 causes transdifferentiation rather than stable dedifferentiation in vivo, suggesting that inactivation of both active and latent differentiation programs are required for tumors to reach a primitive, dedifferentiated state.
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| Overall design |
ChIP-seq data from murine lung adenocarcinomas on (i) transcription factors Nkx2-1 and Foxa in Nkx2-1-deleted tumors and Nkx2-1-positive control tumors, and (ii) four histone marks in Nkx2-1-deleted tumors and Nkx2-1-positive control tumors. (All samples in duplicate and with input controls, i.e. (2 x [(3+3) + (2+8)]) - 1 = 31 samples total - 1 input control used for transcription factor and histone mark, GSM1059357)
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| Contributor(s) |
Snyder EL, Watanabe H, Magendantz M, Hoersch S, Chen TA, Wang DG, Crowley D, Whittaker CA, Meyerson M, Kimura S, Jacks T |
| Citation(s) |
23523371 |
| Submission date |
Jan 02, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Sebastian Hoersch |
| Organization name |
Massachusetts Institute of Technology
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| Department |
David H. Koch Institute for Integrative Cancer Research at MIT
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| Lab |
Bioinformatics and Computing Core
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| Street address |
77 Massachusetts Avenue (E18-366)
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02474 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (31)
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| GSM1059354 |
Transcription factor #1: Nkx2-1, rep. #1 |
| GSM1059355 |
Transcription factor #1: Nkx2-1, rep. #2 |
| GSM1059356 |
Transcription factor #1: input, rep. #1 |
| GSM1059357 |
Transcription factor #1: input, rep. #2 and Histone mark #1-4: input (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059358 |
Transcription factor #2: Foxa1/2 (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059359 |
Transcription factor #2: Foxa1/2 (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059360 |
Transcription factor #2: input, rep. #1 |
| GSM1059361 |
Transcription factor #2: input, rep. #2 |
| GSM1059362 |
Transcription factor #3: Foxa1/2 (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059363 |
Transcription factor #3: Foxa1/2 (Nkx2-1-neg. tumor), rep. #2 |
| GSM1059364 |
Transcription factor #3: input, rep. #1 |
| GSM1059365 |
Transcription factor #3: input, rep. #2 |
| GSM1059366 |
Histone mark #1: H3K27ac (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059367 |
Histone mark #2: H3K27me3 (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059368 |
Histone mark #3: H3K4me1 (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059369 |
Histone mark #4: H3K4me3 (Nkx2-1-pos. tumor), rep. #1 |
| GSM1059370 |
Histone mark #1: H3K27ac (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059371 |
Histone mark #2: H3K27me3 (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059372 |
Histone mark #3: H3K4me1 (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059373 |
Histone mark #4: H3K4me3 (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059374 |
Histone mark #1-4: input (Nkx2-1-pos. tumor), rep. #2 |
| GSM1059375 |
Histone mark #5: H3K27ac (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059376 |
Histone mark #6: H3K27me3 (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059377 |
Histone mark #7: H3K4me1 (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059378 |
Histone mark #8: H3K4me3 (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059379 |
Histone mark #5-8: input (Nkx2-1-neg. tumor), rep. #1 |
| GSM1059380 |
Histone mark #5: H3K27ac (Nkx2-1-neg. tumor), rep. #2 |
| GSM1059381 |
Histone mark #6: H3K27me3 (Nkx2-1-neg. tumor), rep. #2 |
| GSM1059382 |
Histone mark #7: H3K4me1 (Nkx2-1-neg. tumor), rep. #2 |
| GSM1059383 |
Histone mark #8: H3K4me3 (Nkx2-1-neg. tumor), rep. #2 |
| GSM1059384 |
Histone mark #5-8: input (Nkx2-1-neg. tumor), rep. #2 |
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| Relations |
| SRA |
SRP017753 |
| BioProject |
PRJNA185285 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43252_RAW.tar |
13.5 Gb |
(http)(custom) |
TAR (of BED, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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