Microbiota-sensitive epigenetic signature predicts inflammation in Crohn's disease

JCI Insight
Daniel KellyTheresa Alenghat

Abstract

Altered response to the intestinal microbiota strongly associates with inflammatory bowel disease (IBD); however, how commensal microbial cues are integrated by the host during the pathogenesis of IBD is not understood. Epigenetics represents a potential mechanism that could enable intestinal microbes to modulate transcriptional output during the development of IBD. Here, we reveal a histone methylation signature of intestinal epithelial cells isolated from the terminal ilea of newly diagnosed pediatric IBD patients. Genes characterized by significant alterations in histone H3-lysine 4 trimethylation (H3K4me3) showed differential enrichment in pathways involving immunoregulation, cell survival and signaling, and metabolism. Interestingly, a large subset of these genes was epigenetically regulated by microbiota in mice and several microbiota-sensitive epigenetic targets demonstrated altered expression in IBD patients. Remarkably though, a substantial proportion of these genes exhibited H3K4me3 levels that correlated with the severity of intestinal inflammation in IBD, despite lacking significant differential expression. Collectively, these data uncover a previously unrecognized epigenetic profile of IBD that can be primed by com...Continue Reading

References

May 3, 2000·The Journal of Experimental Medicine·K LakyL Puddington
Jun 7, 2000·The Journal of Clinical Investigation·C Booth, C S Potten
Mar 26, 2005·Science·Thomas T Macdonald, Giovanni Monteleone
Nov 18, 2006·Nature Immunology·Jörg H FritzStephen E Girardin
Feb 13, 2007·Immunological Reviews·Stephanie DahanLloyd Mayer
Mar 3, 2007·The Journal of Clinical Investigation·Warren StroberPeter Mannon
May 15, 2007·Lancet·Daniel C Baumgart, Simon R Carding
Nov 6, 2007·Molecular Immunology·Nigel SharfeChaim M Roifman
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Apr 9, 2009·Current Opinion in Infectious Diseases·Christopher D Packey, R Balfour Sartor
May 26, 2009·Nucleic Acids Research·Jing ChenAnil G Jegga
Jun 23, 2009·Annals of the New York Academy of Sciences·Kimberley Lewis, Derek M McKay
Nov 12, 2009·Current Gastroenterology Reports·David Q Shih, Stephan R Targan
Feb 12, 2010·Cold Spring Harbor Protocols·Suresh CuddapahKeji Zhao
Jun 22, 2010·Inflammatory Bowel Diseases·Eric I BenchimolAnne M Griffiths
Aug 7, 2010·European Journal of Immunology·Shabnam ShalapourThomas Schüler
Jan 29, 2011·Journal of Inflammation·Loukia G TsaprouniNeville Punchard
Mar 23, 2011·Nature Immunology·Harald RenzDirk Haller
Apr 13, 2011·Current Opinion in Gastroenterology·Lulu SunThaddeus S Stappenbeck
Sep 22, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric L CampbellSean P Colgan
Sep 29, 2011·Neuroimmunomodulation·Juan Jose MuñozAgustin Zapata
Oct 11, 2011·Cellular and Molecular Life Sciences : CMLS·Arthur KaserRichard S Blumberg
Nov 16, 2011·Database : the Journal of Biological Databases and Curation·Arek Kasprzyk
Mar 16, 2012·Inflammatory Bowel Diseases·James CookeMiles Parkes
Apr 14, 2012·Nature Reviews. Drug Discovery·Cheryl H ArrowsmithMatthieu Schapira
Jun 8, 2012·Science Translational Medicine·Richard Blumberg, Fiona Powrie
Sep 14, 2012·Nature·Valentina Tremaroli, Fredrik Bäckhed
Dec 10, 2013·Molecular Medicine Reports·Jin-Han BaeUNKNOWN IBD Study Group of Korean Association for Study of Intestinal Diseases (KASID)
Feb 26, 2014·Nature Reviews. Immunology·Lance W Peterson, David Artis
Jul 9, 2014·The Journal of Clinical Investigation·Yael HabermanLee A Denson
Dec 9, 2014·Cell Adhesion & Migration·Bethany E Perez White, Spiro Getsios
Jan 31, 2015·Nature Methods·Wolfgang HuberMartin Morgan
Aug 8, 2015·Genome Biology·Andrey V Kartashov, Artem Barski

❮ Previous
Next ❯

Citations

Mar 3, 2019·International Journal of Molecular Sciences·Nathalie AcevedoDaniel P Potaczek
Feb 20, 2020·Current Opinion in Allergy and Clinical Immunology·Ioana AgacheLiliana Rogozea
Jun 4, 2020·Genetics, Selection, Evolution : GSE·Andrew S MasonJacqueline Smith
Jul 25, 2019·Frontiers in Genetics·Bruno Ramos-MolinaFrancisco J Tinahones
Dec 16, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Yinghui ZhaoAjay Goel
Jan 30, 2020·Molecular Metabolism·Rachel Fellows, Patrick Varga-Weisz
May 5, 2020·Current Drug Targets·Agata BiniendaMaciej Salaga
Apr 17, 2021·Environmental Science and Pollution Research International·Amr El-SayedMohamed Kamel
May 14, 2021·Clinical Epigenetics·M HornschuhJ Däbritz
Jun 6, 2021·Cell Death and Differentiation·Robyn Laura KosinskySteven A Johnsen
Jul 31, 2021·BMC Medical Genomics·Ranjit PeliaSubra Kugathasan
May 16, 2021·Journal of Gastroenterology and Hepatology·Ping ChenMei Ye
Oct 27, 2021·Cellular and Molecular Gastroenterology and Hepatology·Chnasu LeeSung Noh Hong

❮ Previous
Next ❯

Methods Mentioned

BETA
IECs
ChIP
ChIP-seq
whether
RNA-seq
biopsies
IEC
biopsy

Software Mentioned

PrepX PolyA script
THOR
ClueGo
Bowtie
PscanChIP
Illumina
TopHat2
Cytoscape
edgeR Bioconductor
DisGeNET

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.