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| Status |
Public on Dec 31, 2014 |
| Title |
Sox4 regulates proliferation, differentiation, and DNA methylation patterns in the intestinal epithelium |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Intestinal stem cells (ISCs) are responsible for maintaining the physiological function of the intestinal epithelium through the production of differentiated absorptive and secretory cellular lineages. In addition to producing specialized functional cells, ISCs must also drive constant proliferation in order to maintain the especially high rate of cellular turnover in the intestinal epithelium, which undergoes near total renewal every 5-7 days. Understanding the transcriptional mechanisms that control how ISCs and transit-amplifying progenitors (TAs) balance differentiation and proliferation in the intestine may provide valuable insight into common pathologies, such as inflammatory bowel disease and cancer. Here, we show that the Sry¬¬-box containing transcription factor, Sox4, is involved in the regulation of proliferation in the ISC/TA zone, the expression of ISC-associated genes, and the differentiation of enteroendocrine (EE) cells. Interestingly, we also observed a significant reduction in the expression of the methylcytosine dioxygenase, Tet1, in Sox4-deficient intestines. We find that Tet1, which initiates derepression of target genes via DNA demethylation, is specifically upregulated in ISC populations in wild-type animals. Additionally, Sox4-deficient intestines showed a significant reduction in levels of 5-hydroxymethylcytosine, the catalytic byproduct of TET protein activity, in the ISC/TA zone. Together, our data demonstrate that Sox4 regulates differentiation and proliferation in the intestinal epithelium, and suggests that it may influence these processes through induction of Tet1 and subsequent derepression of target genes through epigenetic mechanisms.
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| Overall design |
reference x sample
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| Contributor(s) |
Gracz AD, Trotier DC, McCann JV, Harrell CJ, Magness ST |
| Citation missing |
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| Submission date |
Nov 22, 2013 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
cperou@med.unc.edu
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| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
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| Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA230560 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE52675_RAW.tar |
7.9 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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