Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Patterns of chromatin accessibility and transcription factor binding in human and chimpanzee pluripotent stem cells. (#446)

Irene Gallego Romero 1 2 , Shyam Gopalakrishnan 3 , Yoav Gilad 4
  1. School of Biological Sciences, Nanyang Technological University, Singapore
  2. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  3. Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark
  4. Department of Human Genetics, University of Chicago, Chicago, IL, USA

Evolutionary change in closely related species has long been hypothesised to be driven by changes in gene regulation. 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), as well as identified patterns of transcription factor (TF) binding activity across 1261 TFs in the same cell lines. We observe that sharing of chromatin accessibility patterns between the two species is strongest near orthologous transcription start sites (orthoTSS), and decreases with increasing distance from these. However, when we combine these data with a previously published RNA-sequencing dataset from the same cell lines, we find that significant inter-species differences in chromatin accessibility near orthoTSS cannot explain the majority of differentially expressed genes between the two species. Similarly, when we focus on transcription factor binding patterns across the two species, we find that sites most likely to bound in both species tend to have high PWM scores and are located close to orthoTSS. 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.