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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 13, 2018 |
| Title |
DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease (BiSulfite-seq) |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMC) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMC are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wild type littermates, have shortened GI tracts, lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around post-natal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both ¬Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue.
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| Overall design |
mRNA and DNA methyation profiles of Dnmt1 WT and KO jejunum smooth muscle were generated by deep sequencing using Illumina Hiseq2000.
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| Contributor(s) |
Jorgensen BG, Berent RM, Ha SE, Horiguchi K, Sasse KC, Becker LS, Ro S |
| Citation(s) |
29700293 |
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| Submission date |
Jan 25, 2018 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Seungil Ro |
| E-mail(s) |
sro@medicine.nevada.edu
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| Phone |
775-784-1462
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| Organization name |
University of Nevada School of Medicine
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| Department |
Physiology and Cell Biology
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| Street address |
1664 North Virginia St
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| City |
Reno |
| State/province |
NV |
| ZIP/Postal code |
89557 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE109274 |
DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease |
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| Relations |
| BioProject |
PRJNA431590 |
| SRA |
SRP131387 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE109641_RAW.tar |
4.2 Gb |
(http)(custom) |
TAR (of BB) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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