Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1

Yin Yang 1 (YY1) is a multifunctional protein with regulatory potential in tumorigenesis. Ample studies demonstrated the activities of YY1 in regulating gene expression and mediating differential protein modifications. However, the mechanisms underlying YY1 gene expression are relatively understudied. G-quadruplexes (G4s) are four-stranded structures or motifs formed by guanine-rich DNA or RNA domains. The presence of G4 structures in a gene promoter or the 5'-UTR of its mRNA can markedly affect its expression. In this report, we provide strong evidence showing the presence of G4 structures in the promoter and the 5'-UTR of YY1. In reporter assays, mutations in these G4 structure forming sequences increased the expression of Gaussia luciferase (Gluc) downstream of either YY1 promoter or 5'-UTR. We also discovered that G4 Resolvase 1 (G4R1) enhanced the Gluc expression mediated by the YY1 promoter, but not the YY1 5'-UTR. Consistently, G4R1 binds the G4 motif of the YY1 promoter in vitro and ectopically expressed G4R1 increased endogenous YY1 levels. In addition, the analysis of a gene array data consisting of the breast cancer samples of 258 patients also indicates a significant, positive correlation between G4R1 and YY1 expression.     

A novel lncRNA BADLNCR1 inhibits bovine adipogenesis by repressing GLRX5 expression

Adipogenesis is a complex cellular process, which needs a series of molecular events, including long non‐coding RNA (lncRNA). In the present study, a novel lncRNA named BADLNCR1 was identified as a regulator during bovine adipocyte differentiation, which plays an inhibitory role in lipid droplet formation and adipogenic marker gene expression. CHIPR‐seq data demonstrated a potential competitive binding motif between BADLNCR1 and sterol regulatory element‐binding proteins 1 and 2 (SREBP1/2). Dual‐luciferase reporter assay indicated target relationship between KLF2 and BADLNCR1. Moreover, after the induction of KLF2, the expression of adipogenic gene reduced, while the expression of BADLNCR1 increased. Real‐time quantitative PCR (qPCR) showed that BADLNCR1 negatively regulated mRNA expression of GLRX5 gene, a stimulator of genes that promoted formation of lipid droplets and expression of adipogenic genes. GLRX5 could partially reverse the effect of BADLNCR1 in bovine adipocyte differentiation. Dual‐luciferase reporter assay stated that BADLNCR1 significantly reduced the enhancement of C/EBPα on promoter activity of GLRX5 gene. Furthermore, CHIP‐PCR and CHIRP‐PCR confirmed the suppressing effect of BADLNCR1 on binding of C/EBPα to GLRX5 promoter. Collectively, this study revealed the molecular mechanisms underlying the negative regulation of BADLNCR1 in bovine adipogenic differentiation.