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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 17, 2010 |
| Title |
Histone methylation and transcription factor binding during intestinal cell differentation |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by array
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| Summary |
Cell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
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| Overall design |
H3K4me2, CDX2, GATA6, and HNF4A ChIP-seq patterns were mapped in proliferating and 26 day post-confluent (differentatied) Caco-2 intestinal cell lines and compared to published expression data or newly generated Cdx2 knockout mouse intestine expression data
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| Contributor(s) |
Shivdasani RA, Liu XS, Shin H, Verzi MP |
| Citation(s) |
21074721 |
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| Submission date |
Aug 05, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Michael P Verzi |
| Organization name |
Rutgers, the State University of New Jersey
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| Department |
Genetics
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| Lab |
Verzi
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| Street address |
145 Bevier Road
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| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL10773 |
[Mouse430_2_Mm_REFSEQ] Affymetrix GeneChip Mouse Genome 430 2.0 Array [Brainarray Version 12] |
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| Samples (17)
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| Relations |
| SRA |
SRP003411 |
| BioProject |
PRJNA131107 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23436_RAW.tar |
964.6 Mb |
(http)(custom) |
TAR (of BED, BW, CEL, TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Processed data included within Sample table |
| Raw data are available in SRA |
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