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A compendium map of Cis-Regulatory Elements in the Pig Genome and epigenetic comparison with the human Genome

ABSTRACT: Although major advances in genomics have initiated an exciting new era of research, the lack of information about cis-regulatory elements has limited the genetic improvement or manipulation of pig as meat source and biomedical model. Here, we systematically characterize the cis-regulatory elements and their functions in the pig genome in 12 diverse tissues from 4 pig breeds through RNA-Seq, ATAC-Seq, and ChIP-Seq analyses. In total, we generated 199 datasets and identified more than 220,000 pig cis-regulatory elements. We find that cis-regulatory elements are more conserved between humans and pigs than that between humans and mice. To further explore the three dimension structure of pig genome, we performed high-throughput chromosome conformation capture (Hi-C) experiment. The rearrangements of TADs between pig and human have apparently contributed to the evolution of head and face phenotypes. Beyond generating a major new benchmark resource for pig epigenetics research, our study provides basic epigenetic comparative data for using pig as a model for human biomedical research.

ORGANISM(S): Sus scrofa

PROVIDER: GSE143288 | GEO | 2021/02/26

REPOSITORIES: GEO

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Project description:Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects on gene expression are due to nearby genetic variants, trans effects are due to distal genetic variants that affect diffusible elements such as transcription factors. However, as previous studies have mostly assessed the impacts of cis and trans effects at the gene level, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we used massively parallel reporter assays to directly measure cis and trans effects between human and mouse embryonic stem cells at thousands of individual regulatory elements, including enhancers as well as promoters of both protein-coding and long non-coding RNA genes. Our approach revealed that cis effects are widespread across regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we found that trans effects are rare but stronger in enhancers than promoters, and can be attributed to a subset of transcription factors that are differentially expressed between human and mouse. While previous gene-based studies have found extensive co-occurrence of cis and trans effects in opposite directions that stabilize gene expression between species—or compensatory cis-trans effects—we find that cis-trans compensation is uncommon within individual regulatory elements. Moreover, regulatory elements that do show compensatory cis-trans effects are often less redundant than regulatory elements lacking compensatory cis-trans effects. Thus, our results are consistent with a model wherein compensatory cis-trans effects occur more often through crosstalk between multiple redundant regulatory elements than within a single individual regulatory element. Together, these results indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.

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A compendium map of Cis-Regulatory Elements in the Pig Genome and epigenetic comparison with the human Genome

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