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

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DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon. / Fazio, Antonella; Bordoni, Dora; Kuiper, Jan W P; Weber-Stiehl, Saskia; Stengel, Stephanie T; Arnold, Philipp; Ellinghaus, David; Ito, Go; Tran, Florian; Messner, Berith; Henning, Anna; Bernardes, Joana P; Häsler, Robert; Luzius, Anne; Imm, Simon; Hinrichsen, Finn; Franke, Andre; Huber, Samuel; Nikolaus, Susanna; Aden, Konrad; Schreiber, Stefan; Sommer, Felix; Natoli, Gioacchino; Mishra, Neha; Rosenstiel, Philip.

in: NAT COMMUN, Jahrgang 13, 6266, 21.10.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fazio, A, Bordoni, D, Kuiper, JWP, Weber-Stiehl, S, Stengel, ST, Arnold, P, Ellinghaus, D, Ito, G, Tran, F, Messner, B, Henning, A, Bernardes, JP, Häsler, R, Luzius, A, Imm, S, Hinrichsen, F, Franke, A, Huber, S, Nikolaus, S, Aden, K, Schreiber, S, Sommer, F, Natoli, G, Mishra, N & Rosenstiel, P 2022, 'DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon', NAT COMMUN, Jg. 13, 6266. https://doi.org/10.1038/s41467-022-33844-2

APA

Fazio, A., Bordoni, D., Kuiper, J. W. P., Weber-Stiehl, S., Stengel, S. T., Arnold, P., Ellinghaus, D., Ito, G., Tran, F., Messner, B., Henning, A., Bernardes, J. P., Häsler, R., Luzius, A., Imm, S., Hinrichsen, F., Franke, A., Huber, S., Nikolaus, S., ... Rosenstiel, P. (2022). DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon. NAT COMMUN, 13, [6266]. https://doi.org/10.1038/s41467-022-33844-2

Vancouver

Fazio A, Bordoni D, Kuiper JWP, Weber-Stiehl S, Stengel ST, Arnold P et al. DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon. NAT COMMUN. 2022 Okt 21;13. 6266. https://doi.org/10.1038/s41467-022-33844-2

Bibtex

@article{160e2fe07c6942e79cbe252dd52bd4b6,
title = "DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon",
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.",
keywords = "Humans, Mice, Animals, Caco-2 Cells, DNA Methyltransferase 3A, Intestinal Mucosa/metabolism, Colon/pathology, Epithelial Cells/metabolism, Inflammatory Bowel Diseases/pathology, Tumor Necrosis Factors/metabolism, DNA/metabolism",
author = "Antonella Fazio and Dora Bordoni and Kuiper, {Jan W P} and Saskia Weber-Stiehl and Stengel, {Stephanie T} and Philipp Arnold and David Ellinghaus and Go Ito and Florian Tran and Berith Messner and Anna Henning and Bernardes, {Joana P} and Robert H{\"a}sler and Anne Luzius and Simon Imm and Finn Hinrichsen and Andre Franke and Samuel Huber and Susanna Nikolaus and Konrad Aden and Stefan Schreiber and Felix Sommer and Gioacchino Natoli and Neha Mishra and Philip Rosenstiel",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = oct,
day = "21",
doi = "10.1038/s41467-022-33844-2",
language = "English",
volume = "13",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon

AU - Fazio, Antonella

AU - Bordoni, Dora

AU - Kuiper, Jan W P

AU - Weber-Stiehl, Saskia

AU - Stengel, Stephanie T

AU - Arnold, Philipp

AU - Ellinghaus, David

AU - Ito, Go

AU - Tran, Florian

AU - Messner, Berith

AU - Henning, Anna

AU - Bernardes, Joana P

AU - Häsler, Robert

AU - Luzius, Anne

AU - Imm, Simon

AU - Hinrichsen, Finn

AU - Franke, Andre

AU - Huber, Samuel

AU - Nikolaus, Susanna

AU - Aden, Konrad

AU - Schreiber, Stefan

AU - Sommer, Felix

AU - Natoli, Gioacchino

AU - Mishra, Neha

AU - Rosenstiel, Philip

N1 - © 2022. The Author(s).

PY - 2022/10/21

Y1 - 2022/10/21

N2 - 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.

AB - 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.

KW - Humans

KW - Mice

KW - Animals

KW - Caco-2 Cells

KW - DNA Methyltransferase 3A

KW - Intestinal Mucosa/metabolism

KW - Colon/pathology

KW - Epithelial Cells/metabolism

KW - Inflammatory Bowel Diseases/pathology

KW - Tumor Necrosis Factors/metabolism

KW - DNA/metabolism

U2 - 10.1038/s41467-022-33844-2

DO - 10.1038/s41467-022-33844-2

M3 - SCORING: Journal article

C2 - 36271073

VL - 13

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

M1 - 6266

ER -