Transcriptional regulation of olfactory receptor OR51B5 by the TBX6

Olfactory receptors (ORs) are G protein-coupled receptors primarily expressed in olfactory tissue, facilitating the perception of odors. Interestingly, they have also been detected in nonolfactory tissues such as the skin, where they regulate processes like collagen synthesis. This study aimed to analyze the promoter of the OR family 51 subfamily B member 5 (OR51B5) and identify the transcription factors that bind to it to understand the potential regulatory mechanisms for OR51B5 expression. We examined the promoter region spanning 2,000 base pairs upstream of the transcription start site and conducted a deletion analysis, revealing that the core promoter encompasses the region from -153 to -111 base pairs. A luciferase assay using various candidate transcription factors showed that the overexpression or knockdown of T-Box Transcription Factor 6 (TBX6) significantly regulated OR51B5 promoter activity, whereas other candidate transcription factors had no significant effect. In addition, we validated TBX6 binding to the OR51B5 promoter using site-directed mutation and electrophoretic mobility shift assays, and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR). This study is the first to uncover the role of TBX transcription factors in regulating OR gene expression in mammals, which may have implications for treating related disorders.<b>NEW & NOTEWORTHY</b> This study reveals that olfactory receptor OR51B5, primarily known for its role in olfaction, is significantly regulated by the transcription factor TBX6 in nonolfactory tissues. We demonstrate that TBX6 binding to the OR51B5 promoter modulates its activity, highlighting a novel regulatory mechanism for olfactory receptor expression, which could impact collagen synthesis and cell survival in human dermal fibroblasts.