Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes

Nucleic Acids Research
Isha SethiSatrajit Sinha

Abstract

Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of ∼1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost ...Continue Reading

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Datasets Mentioned

BETA
GSE17611
GSE86902

Methods Mentioned

BETA
transgenic
immunoprecipitation
ChIP-Seq
ChIPs
DNA-seq
RNA-Seq
ChIP

Software Mentioned

GREAT
MSigDB
Ensembl Genome
CentriMo
MEME
Bowtie
UCSC liftover tool
MACS2
Biomart
PhyloP

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