BMC Seminar Thursday 4th of January at 12:00 in room 343 Læknagarður

Speaker: Dr. Katla Kristjánsdóttir, postdoc at Cornell University, NY

Title: Variation in regulatory element transcription: architecture and interactions

Abstract: The vast majority of disease associated genetic variants (single nucleotide polymorphisms; SNPs) fall within regulatory regions of the genome. To understand how such SNPs contribute to disease, we need to uncover how underlying sequences affect the function of transcriptional regulatory elements (TREs), such as enhancers and promoters. TREs share a common architecture, consisting of a central transcription factor (TF) binding region flanked by sites of transcription. This transcriptional architecture can be used to identify active TREs; the amount of transcription directly relates to regulatory activity. Apart from the functional gene product, the RNAs produced are generally unstable and therefore difficult to detect using steady-state RNA sequencing. Precision nuclear run-on sequencing with 5´-cap enrichment (PRO-cap) quantifies transcriptional activity by sequencing nascent RNAs. Using PRO-cap in 69 human lymphoblastoid cell lines, we identify over eighty thousand transcribed transcriptional regulatory elements (tTREs). We then map genotypes to variation in the level and strandedness of transcription initiation and find thousands of SNPs that associate with tTRE transcription. Many of these SNPs overlap with SNPs that associate with gene expression and they are enriched at specific positions within the tTREs, hinting at potential mechanisms. Finally, we use tTRE co-expression analyses to explore interactions between tTREs. Specifically, we examine the role of TFs in modulating mid-range interactions and the strand-specificity of interactions at closely-spaced tTREs.

Bio: Katla studied biochemistry here at the University of Iceland, during which time she worked in the labs of Dr. Guðmundur H. Guðmundsson, Dr. Eiríkur Steingrímsson, and Dr. Stefán Þ. Sigurðsson, as well as doing a summer research internship at Caltech. She then moved to Ithaca NY to do her PhD at Cornell University, where she studied post-transcriptional gene regulation in the Grimson lab. After graduating she moved on to study transcriptional gene regulation in the Kwak lab at Cornell, where she is now a postdoc.