Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal disorder, with two main types: Crohn’s disease (CD) and ulcerative colitis (UC), whose molecular pathology is not well-understood. The majority of IBD-associated SNPs are located in non-coding regions and are hard to characterize since regulatory regions in IBD are not known.
Using CAGE-seq, we profiled transcription start sites (TSSs) and transcribed enhancers of biopsies taken from the descending colon of 94 IBD patients and controls. This allowed for the identification of IBD-induced TSSs and enhancers, and the relation of these regions to IBD-associated genetic variations.
We found that IBD-upregulated promoters and enhancers were highly enriched for IBD-associated SNPs and were bound by the same transcription factors. We also identify enhancers clusters upregulated in the disease, which seem to have different functions from similarly upregulated singleton enhancers. IBD-specific TSSs were associated to genes with roles in both inflammatory cascades and gut epithelia: TSSs distinguishing UC and CD were associated to gut epithelia functions. Using a combination of CAGE, nanofluidics qPCR and machine learning, we identified 35 TSSs that could distinguish active CD, UC and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation and genetics of IBD.
Meet the speaker
If you want to meet Dr. Albin Sandelin, please book a time slot at https://doodle.com/poll/4gdvez8bgk7m3xc9 and send an email to anthony.mathelier@ncmm.uio.no.
Website
albinsandelin.wixsite.com/sandelinlab
Junior talk
Dr. Sandelin's lecture will be preceded by a talk by Dr. Bastian Fromm, postdoctoral fellow at the Institute for Cancer Research, Oslo University Hospital, entitled "What makes a microRNA? - old and new insights from the curation of 32 metazoan genomes.".