Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research. Enhancers are critical regulatory elements that have fundamental functions in evolution, development and disease. Genome-wide quantification of functional enhancers in the pig is needed. Results:We performed self-transcribing active regulatory region sequencing (STARR-seq) in the porcine kidney epithelial PK15 and testicular ST cell lines, and reliably identified 2576 functional enhancers. Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes. Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3, which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones. This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages. Additionally, the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers. Conclusions:In summary, we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.

Yinqiao Wu;Yuedong Zhang;Hang Liu;Yun Gao;Yuyan Liu;Ling Chen;Lu Liu;David M.Irwin;Chunhui Hou;Zhongyin Zhou;Yaping Zhang

State Key Laboratory of Genetic Resources and Evolution,and Yunnan Laboratory of Molecular Biology of Domestic Animals,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,Yunnan,China;Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming 650204,Yunnan,China;State Key Laboratory for Conservation and Utilization of Bio-resource in Yunnan,Yunnan University,Kunming 650091,Yunnan,China;School of Life Science,Yunnan University,Kunming 650091,Yunnan,China;Institute of Physical Science and Information Technology,Anhui University,Hefei 230601,Anhui,China;Department of Laboratory Medicine and Pathobiology,University of Toronto,Toronto,Canada;Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China;Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,Yunnan,China

畜牧与生物技术杂志（英文版）

[1]Yinqiao Wu;Yuedong Zhang;Hang Liu;Yun Gao;Yuyan Liu;Ling Chen;Lu Liu;David M.Irwin;Chunhui Hou;Zhongyin Zhou;Yaping Zhang-.Genome-wide identification of functional enhancers and their potential roles in pig breeding)[J].畜牧与生物技术杂志（英文版）,2022(06):1690-1702

Enhancers,transcribing,H3K4me1

Genome,identification,functional,enhancers,their,potential,roles,pig,breeding,Background,economically,important,livestock,species,widely,applied,large,animal,model,medical,research,critical,regulatory,elements,that,have,fundamental,functions,evolution,disease,quantification,needed,Results,We,performed,self,active,sequencing,STARR,porcine,kidney,epithelial,PK15,testicular,lines,reliably,identified,Most,these,were,located,repetitive,sequences,enriched,within,silent,lowly,expressed,genes,poorly,overlapped,chromatin,accessibility,regions,highly,repressive,modification,H3K9me3,which,different,from,predicted,detected,using,ChIP,H3K27ac,modified,histones,This,suggests,most,endogenously,repressed,level,may,during,type,specific,developmental,stages,Additionally,PPP3CA,associated,loin,muscle,area,trait,QKI,alkaline,phosphatase,activity,be,regulated,by,distal,Conclusions,In,summary,generated,first,map,cells,genome,highlight,its

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