BMC-GPMLS: Distinguished lecture series
Prof. Albin Sandelin, University of Copenhagen
Title: The transcription start site and enhancer landscape of the descending colon in inflammatory bowel disease
Time: Thursday, Oct. 27th, 16:00-17:00
Location: HT-103 (Háskólatorgi)
Coordinated gene regulation is essential for all aspects of cell biology, including development, differentiation and disease. Characterization of enhancers and promoters in disease has been difficult due to the lack of genome-wide methods suitable for the analysis of small tissue samples. Therefore, we know little about the regulation of genes in disease, and its variation between patients.
Because both promoter and enhancers are transcribed, they can be detected by RNA sequencing. Utilizing this, we have profiled promoter and enhancer usage in patients suffering from inflammatory bowel disease (IBD), a complex group of chronic inflammatory conditions in the gut. Crohn’s disease (CD) and Ulcerative Colitis (UC) are the two principal subtypes. Correct treatment depends on accurate sub-type diagnosis, which is challenging and expensive.
To this end, we have profiled the descending colon of 100 human subjects, stratified into disease subtypes and controls. We identified a promoter set that with high accuracy can distinguish the shared inflammatory response, and UC-or CD patient-specific responses. These included annotated promoters, alternative promoters and promoters of novel long non-coding RNAs.
Moreover, we identified over 10.000 enhancer regions that are active in these samples, where subsets are induced in general inflammation or in UC/CD specifically. These enhancers are often linked to known and novel IBD-induced genes, suggesting that they are important in the pathogenesis. Connected to this, IBD-associated SNPs were highly enriched in these regulatory regions, enabling subsequent identification of casual regulatory mutations.
To our knowledge, this is the first comprehensive profiling of enhancers and promoters in large patient cohorts for any disease.