DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon

Antonella Fazio, Dora Bordoni, Jan W. P. Kuiper, Saskia Weber-Stiehl, Stephanie T. Stengel, Philipp Arnold, David Ellinghaus, Go Ito, Florian Tran, Berith Messner, Anna Henning, Joana P. Bernardes, Robert Häsler, Anne Luzius, Simon Imm, Finn Hinrichsen, Andre Franke, Samuel Huber, Susanna Nikolaus, Konrad Aden, Stefan Schreiber, Felix Sommer, Gioacchino Natoli, Neha Mishra and Philip Rosenstiel ()
Additional contact information
Antonella Fazio: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Dora Bordoni: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Jan W. P. Kuiper: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Saskia Weber-Stiehl: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Stephanie T. Stengel: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Philipp Arnold: Friedrich-Alexander-University Erlangen-Nürnberg (FAU)
David Ellinghaus: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Go Ito: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Florian Tran: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Berith Messner: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Anna Henning: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Joana P. Bernardes: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Robert Häsler: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Anne Luzius: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Simon Imm: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Finn Hinrichsen: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Andre Franke: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Samuel Huber: University Medical Center Hamburg-Eppendorf
Susanna Nikolaus: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Konrad Aden: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Stefan Schreiber: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Felix Sommer: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Gioacchino Natoli: European Institute of Oncology IRCCS (IEO)
Neha Mishra: Christian-Albrechts-University and University Hospital Schleswig-Holstein
Philip Rosenstiel: Christian-Albrechts-University and University Hospital Schleswig-Holstein

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Genetic variants in the DNA methyltransferase 3 A (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 from IBD patients and upon tumor necrosis factor 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 intestinal epithelial cells (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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33844-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33844-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33844-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().