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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 21, 2022 |
| Title |
DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon [Array] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Genetic variants in the DNMT3A locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function. DNMT3A expression is downregulated in intestinal epithelial cells (IECs) from IBD patients and upon TNF treatment in murine intestinal organoids. Ablation of DNMT3A in Caco-2 cells results in global DNA hypomethylation, which is linked to impaired regenerative capacity, transepithelial resistance and intercellular junction formation. Genetic deletion of Dnmt3a in IECs (Dnmt3aΔIEC) in mice confirms the phenotype of an altered epithelial ultrastructure with shortened apical-junctional complexes, reduced Goblet cell numbers and increased intestinal permeability in the colon in vivo. Dnmt3aΔIEC mice suffer from increased susceptibility to experimental colitis, characterized by reduced epithelial regeneration. These data demonstrate a critical role for DNMT3A in orchestrating intestinal epithelial homeostasis and response to tissue damage and suggest an involvement of impaired epithelial DNMT3A function in the etiology of IBD.
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| Overall design |
4 groups of Caco-2 cells were analyzed, each comprising 4 replicates. For baseline condition analysis, purified intestinal epithelial cells from steady state Dnmt3afl/fl (n=3) and Dnmt3a△IEC (n=4) were used. For in vivo DSS experiment, intestinal crypts were obtained from Dnmt3afl/fl and Dnmt3aΔIEC mice at day 5 (peak of disease:n=5 vs 5), and at day 12 (recovery phase: 7 days after DSS treatment:n=8 vs 7)
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| Contributor(s) |
Mishra N, Fazio A, Bordoni D, Rosenstiel P |
| Citation(s) |
36271073 |
| Submission date |
Aug 08, 2022 |
| Last update date |
Nov 02, 2022 |
| Contact name |
Neha Mishra |
| E-mail(s) |
n.mishra@ikmb.uni-kiel.de
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| Organization name |
Institute of Clinical Molecular Biology
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| Lab |
Cell biology Lab
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| Street address |
Rosalind-Franklin-Str. 12
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| City |
Kiel |
| ZIP/Postal code |
24105 |
| Country |
Germany |
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| Platforms (2) |
| GPL21145 |
Infinium MethylationEPIC |
| GPL31950 |
Infinium MouseMethylation285 BeadChip |
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| Samples (48)
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| GSM6435888 |
Caco2, 3A1-4, DNA |
| GSM6435889 |
Caco2, 3A2-1, DNA |
| GSM6435890 |
Caco2, 3A2-2, DNA |
| GSM6435891 |
Caco2, 3A2-3, DNA |
| GSM6435892 |
Caco2, 3A2-4, DNA |
| GSM6435893 |
Caco2, 3AKO-1, DNA |
| GSM6435894 |
Caco2, 3AKO-2, DNA |
| GSM6435895 |
Caco2, 3AKO-3, DNA |
| GSM6435896 |
Caco2, 3AKO-4, DNA |
| GSM6435897 |
Caco2, WT-1, DNA |
| GSM6435898 |
Caco2, WT-2, DNA |
| GSM6435899 |
Caco2, WT-3, DNA |
| GSM6435900 |
Caco2, WT-4, DNA |
| GSM6436762 |
Dnmt3aVillin642, DNA |
| GSM6436763 |
Dnmt3aVillin643, DNA |
| GSM6436764 |
Dnmt3aVillin655, DNA |
| GSM6436765 |
Dnmt3aVillin656, DNA |
| GSM6436766 |
Dnmt3aVillin657, DNA |
| GSM6436767 |
Dnmt3aVillin660, DNA |
| GSM6436768 |
Dnmt3aVillin661, DNA |
| GSM6436769 |
Dnmt3aVillin662, DNA |
| GSM6436770 |
Dnmt3aVillin663, DNA |
| GSM6436771 |
Dnmt3aVillin666, DNA |
| GSM6436772 |
Dnmt3aVillin667, DNA |
| GSM6436773 |
Dnmt3aVillin668, DNA |
| GSM6436774 |
Dnmt3aVillin670, DNA |
| GSM6436775 |
Dnmt3aVillin672, DNA |
| GSM6436776 |
Dnmt3aVillin673, DNA |
| GSM6436777 |
Dnmt3aVillin674, DNA |
| GSM6436778 |
Dnmt3aVillin675, DNA |
| GSM6436779 |
Dnmt3aVillin677, DNA |
| GSM6436780 |
Dnmt3aVillin678, DNA |
| GSM6436781 |
Dnmt3aVillin683, DNA |
| GSM6436782 |
Dnmt3aVillin684, DNA |
| GSM6436783 |
Dnmt3aVillin690, DNA |
| GSM6436784 |
Dnmt3aVillin691, DNA |
| GSM6436785 |
Dnmt3aVillin692, DNA |
| GSM6436786 |
Dnmt3aVillin693, DNA |
| GSM6436787 |
Dnmt3aVillin718, DNA |
| GSM6436788 |
Dnmt3aVillin719, DNA |
| GSM6436789 |
Dnmt3aVillin720, DNA |
| GSM6436790 |
Dnmt3aVillin721, DNA |
| GSM6436791 |
Dnmt3aVillin722, DNA |
| GSM6436792 |
Dnmt3aVillin723, DNA |
| GSM6436793 |
Dnmt3aVillin724, DNA |
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| This SubSeries is part of SuperSeries: |
| GSE210763 |
DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon |
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| Relations |
| BioProject |
PRJNA867381 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210721_RAW.tar |
548.2 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
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