Int J Biol Sci 2020; 16(15):2964-2973. doi:10.7150/ijbs.47959 This issue
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Detecting selection signatures in genomes that relates to transcription regulation has been challenges in genetic analysis. Here, we report a set of transcription factors EBF1, E2F1 and EGR2 for transcription activation of RAB37 promoter by a comparative analysis of promoter activities of RAB37 in humans, mice, and pigs. Two of the transcription factors bound to and co-regulated RAB37 promoter in each species. SNPs were further screened in pig RAB37 gene by population genomics in pig populations from both China and Europe. Three SNPs were identified in second CpG island upstream of core promoter of RAB37. These SNP variations led to at least 5 haplotypes, representing 5 multiple alleles of RAB37 in pig population. Distribution of these alleles in different genetic background of breeds showed a role of artificial selection for the variations of these multiple alleles. Of them, RAB37-c acquired the highest ability to activate gene expression in comparison with the other promoters, thus enhanced autophagy efficiently. These findings provide better understanding of transcription activation of RAB37 and artificial selection via RAB37 for autophagy regulation.
Keywords: transcription factors, genomic variation, RAB37, SNPs, mammals