MIG Seminar – Irene Gallego Romero – 17th November, 2017

Irene Gallego Romero

Melbourne Integrative Genomics, University of Melbourne

Friday 17th November
12-1pm
FW Jones Theatre, Level 3, Medical Building, The University of Melbourne

Comparative dynamics of transcription factor binding and chromatin accessibility in humans and chimpanzees

Abstract
Many human-specific traits have long been hypothesised to be driven by gene regulatory differences between ourselves and our close evolutionary relatives. To test this hypothesis, we have generated maps of genome-wide chromatin accessibility using ATAC-seq in induced pluripotent stem cell (iPSC) lines derived from 6 humans and 7 chimpanzees (Pan troglodytes, our closest living relative), and quantified patterns of transcription factor (TF) binding activity in over 130 million putative sites across 308 different TFs. As expected, we find that sharing of chromatin accessibility patterns between the two species is strongest near highly conserved orthologous transcription start sites and decreases with distance from orthoTSS. Combining these results with RNA-sequencing data from the same cell lines we find that significant inter-species differences in chromatin accessibility near orthoTSS occur more often than expected at differentially expressed genes, confirming the role of chromatin accessibility as a regulatory mechanism. Similarly, when we focus on transcription factor binding patterns in the two species, we find that TF binding sites most likely to be bound in both species are preferentially located close to orthoTSS and tend to have high position weight matrix (PWM) scores. Intriguingly, some of the transcription factors with the most divergent inter-species binding patterns have been implicated in early developmental processes, suggesting that the differences we observe at the pluripotent stage might underlie other interspecies cellular-level, and potentially even organismal-level, differences between humans and chimpanzees. Taken together, our results suggest that changes in chromatin accessibility and transcription factor activity are a likely gene regulatory mechanism through which human-specific traits can arise.

Bio
See Irene's bio here.

Enquiries: Andrew Siebel (asiebel@unimelb.edu.au)