A novel PAX7 10-bp indel variant modulates promoter activity, gene expression and contributes to different phenotypes of Chinese cattle

Abstract

Paired box 7 (PAX7) gene regulates the conversion of muscle satellite cells into myogenic cells and participates in multi-step processes in myogenesis.Expression levels of PAX7 are decisive for its regulatory function. Previous reports revealed that PAX7 were responsible for the developmental traits of muscle. The relationship of the PAX7 promoter variants and livestock phenotypic traits has not been fully elucidated. We detected a novel 10-bp insertion/deletion (indel) polymorphism in the bovine PAX7 promoter and revealed that the indel altered the binding of the transcriptional factor ZNF219. Luciferase reporter assay showed that deletion-deletion (Del-Del) genotype of the PAX7 gene showed 2.79-fold higher promoter activity than the insertion-insertion (Ins-Ins) genotype (P < 0.05), and ZNF219 overexpression significantly diminished the luciferase activity in Ins-Ins groups. Moreover, the expression of PAX7 and its down-stream genes were detected in fetal skeletal muscle of cattle with different PAX7 genotypes, where the Del-Del genotype also displayed high expression levels. Statistical association analysis demonstrated that this indel had significant effects on early growth traits in cattle. These findings provide a complete overview of the function of the PAX7 10-bp variant, which may have potential as a genetic marker for marker-assisted selection in improving economically significant traits of cattle.Cattle phenotypes of economic significance, such as growth rates, carcass, and meat quality, have attracted much attention from breeders in the beef cattle industry. Such phenotypes constitute a multifactorial background that arises from interactions between environmental and genetic factors 1 . In marker-assisted selection programs, the efficiency of selection is associated with the identification of candidate genes, as well as the exploration of genome-wide variation markers that are responsible for the complex quantitative traits 2 . The establishment of genetic association approach provides a unique opportunity to study genotype-phenotype relationships 3 . Therefore, the integration of screening for variations and gene association programs can improve assessments of the genetic effects of candidate genes, thus providing promising materials for successful genetic selection in cattle breeding.Muscle satellite cells, known as muscle-specific committed progenitors, are located under the basal lamina of muscle fibres and play important roles in the growth, maintenance, homeostasis, repair, and regeneration of skeletal muscle [4][5][6] . Paired box 7 (PAX7) gene, a member of the paired box gene family, is the marker gene of myogenic satellite cells 7 . PAX7 is specifically expressed in quiescent, activated, and proliferating satellite cells, and PAX7-expressing satellite cells are indispensable for the postnatal muscle development and regeneration after the injury of skeletal muscle, however, their regenerative function can not be performed by other endogenous cell

A 20-bp insertion/deletion (indel) polymorphism within the &lt;i&gt;CDC25A&lt;/i&gt; gene and its associations with growth traits in goat

“…It was reported that a multiallelic indel in the promoter region of the Cyclin-dependent Kinase Inhibitor 3 gene was significantly associated with body weight and carcass traits in chickens (Li et al, 2018). A 10-bp indel polymorphism in the bovine PAX7 promoter altered the binding of the transcriptional factor ZNF219 and modulated promoter activity and gene expression in Chinese cattle (Xu et al, 2018). Also, some literature illustrated that both SNP and indel variations were closely related to certain traits, including the growth traits of cashmere goat (Zhang et al, 2015;Wang et al, 2019a).…”

Small RNAs generated by bidirectional transcription mediate silencing of RXLR effector genes in the oomycete Phytophthora sojae

“…A further genome-wide analysis suggests that 9 or 10 -bp INDEL variations were broadly present in the promoter regions of P. sojae genes and were significantly enriched in the RXLR effector genes, suggesting that the oomycete pathogens may have evolved functional cis-elements by promoter INDEL variations to control gene expression, especially for the RXLR effector genes. Consistently, a recent study showed that a natural 10-bp INDEL variant of the PAX7 promoter could regulate gene expression by altering the binding of transcriptional factor ZNF219 in animal cells (Xu et al 2018). Notably, 10 bp is the distance of the double helix per turn in DNA, allowing the distance of cis-elements be easily reprogrammed by INDEL variations.…”

Association of a new 99-bp indel of the CEL gene promoter region with phenotypic traits in chickens

“…In this study, an indel caused by a 99 bp insertion fragment was shown for the first time in the promoter region of the CEL gene. Indel mutations in the promoter region have been found in livestock, suggesting their key role in animal growth and carcass traits 25,26 .…”