Epigenetics, DNA Organization, and Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders affecting the gastrointestinal tract. The incidence of IBD is increasing, with more cases occurring in developed countries. Multiple factors such as genetics, environmental changes, gut microbiota, and immune abnormalities have been associated with development of IBD. In recent years, it has become increasingly apparent that epigenetic modifications of chromatin and the manner in which chromatin is organized in the nucleus are additionally important elements that can influence responses induced by the factors described above, and may therefore contribute to the onset and pathogenesis of IBD. Epigenetics and chromatin organization regulate diverse functions that include maintenance of homeostasis in the intestinal epithelium, the development and differentiation of immune cells, and modulation of responses generated by the immune system to defend against potential pathogens. Furthermore, changes in epigenetic chromatin marks and in chromatin organization have now been linked to differential gene expression in IBD patient cells. Although direct evidence for a role of histone modifications in IBD is currently very limited, in this review, we summarize the links between various epigenetic modifications, the proteins that catalyze or recognize these modifications, and the development or progression of IBD in human and experimental IBD. We also discuss how epigenetics influence the organization of DNA contacts to regulate gene expression and the implications this may have for diagnosing and treating IBD.

Self-care: the way to find balance in life : Development and evaluation of a self-care questionnaire for patients with inflammatory bowel disease

“…Other theories are that gene defects lead to an immunological dysfunction and lost immunological tolerance, resulting in an abnormal immune response to harmless antigens, or that IBD can be triggered by a virus or bacteria (24,25). Gene defects in patients with IBD are associated with functions such as cell cycle and growth, fluid balance in the colon, lipid and lipoprotein metabolism, and the mucosa barrier dysfunction (26,27). Genome-wide association studies identify over 230 genetic loci known to be associated with IBD (28,29).…”

“…Self-care management was described as making sure to sleep well (62%), stress management (73%), finding out more about IBD (79%), and looking for new approaches living with IBD (68%) ( Table 8). 17107 (36) 82 (27) 58 (19) 3 (1) I avoid various activities 109 (36) 124 4149 (16) 12 44 (1) I avoid sex 126 (42) 96 3226 913 436 (12) I avoid alcohol 84 2883 2858 (19) 44 1519 (6) Plan my day so that I am always near a toilet 80 (27) 103 3454 (18) 56 (19) 5 (2) I plan my day in view of the fact that I have IBD 100 (33) 120 4044 (15) 31 104 (1) Do you take medication for IBD as prescribed by a doctor?…”

Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140

“…Epigenetic processes play an important role in the regulation of macrophage differentiation and gene expression, mediated by DNA methylation and histone post-translational modification 7,8 . As such, epigenetic mechanisms mediated through the activity of specific histone acetylases and deacetylases activity are implicated in CD pathogenesis 9,10,11 .…”

Profiling Non-Coding RNA Levels With Clinical Classifiers in Pediatric Crohn’s Disease

“…In ammatory Bowel Disease (IBD) is a disorder affecting the intestines with two prominent disease types; ulcerative colitis (UC) and Crohn's disease (CD), whereby UC is con ned mostly to the colonic mucosa with persistent chronic in ammation 1 and CD is a transmural disease affecting the entire gastrointestinal tract 2 . Rising incidence of IBD have been attributed to the gut-microbiome interactions, genetic predispositions, and environmental triggers 3 , but more recently attention has been placed on epigenetic mechanisms 4 . Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression but can also directly affect protein function, thus having a substantial impact on biological processes 5 .…”