PT - JOURNAL ARTICLE AU - Irene Gallego Romero AU - Shyam Gopalakrishnan AU - Yoav Gilad TI - Widespread conservation of chromatin accessibility patterns and transcription factor binding in human and chimpanzee induced pluripotent stem cells AID - 10.1101/466631 DP - 2018 Jan 01 TA - bioRxiv PG - 466631 4099 - http://biorxiv.org/content/early/2018/11/09/466631.short 4100 - http://biorxiv.org/content/early/2018/11/09/466631.full AB - Changes in gene regulation have been shown to contribute to phenotypic differences between closely related species, most notably in primates. It is likely that a subset of inter-species regulatory differences can be explained by changes in chromatin accessibility and transcription factor binding, yet there is a paucity of comparative data sets with which to investigate this. Using ATAC-seq, we profiled genome-wide chromatin accessibility in a matched set of 6 human and 6 chimpanzee (Pan troglodytes, our closest living relative) induced pluripotent stem cells from which we have previously collected gene expression data. We examined chromatin accessibility patterns near 20,745 orthologous transcriptions start sites and used a footprinting algorithm to predict transcription factor binding activity in each species. We found that the majority of chromatin accessibility patterns and transcription factor activity are conserved between these two closely related species. Interestingly, interspecies divergence in chromatin accessibility and transcription factor binding in pluripotent cells appear to contribute not to differences in the pluripotent state, but to downstream developmental processes. Put together, our findings suggest that the pluripotent state is extremely stable and potentially subject to stronger evolutionary constraint than other somatic tissues.AbbreviationsATACassay for transposase-accessible chromatinCPMcounts per millionDAdifferentially accessibleDEdifferentially expressedESCembryonic stem cellFDRfalse discovery rateiPSCinduced pluripotent stem cellMPBSmotif-predicted binding site(s)PCAprincipal component analysisPWMposition weight matrixRPKMreads per kilobase per million reads mappedTFtranscription factorTFBStranscription factor binding site(s)TSStranscription start site(s)