Usage Information
Citation Information: JCI Insight. 2018;3(18):e122104. https://doi.org/10.1172/jci.insight.122104.
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 commensal microbes and indicate sensitive targets in the epithelium that may underlie how microbiota predispose to subsequent intestinal inflammation and disease.
Authors
Daniel Kelly, Michael Kotliar, Vivienne Woo, Sajjeev Jagannathan, Jordan Whitt, Jessica Moncivaiz, Bruce J. Aronow, Marla C. Dubinsky, Jeffrey S. Hyams, James F. Markowitz, Robert N. Baldassano, Michael C. Stephens, Thomas D. Walters, Subra Kugathasan, Yael Haberman, Nambirajan Sundaram, Michael J. Rosen, Michael Helmrath, Rebekah Karns, Artem Barski, Lee A. Denson, Theresa Alenghat
Usage data is cumulative from September 2023 through September 2024.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,075 | 312 |
| 65 | 63 | |
| Figure | 133 | 9 |
| Table | 17 | 0 |
| Supplemental data | 20 | 8 |
| Citation downloads | 35 | 0 |
| Totals | 1,345 | 392 |
| Total Views | 1,737 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
