Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease

摘要

A Diagram showing a schematic model of the DNA-binding POU domain in Brn-3b TF, which is unique to the POU family of transcription factors. This domain consists of the POUHD which binds to the major groove of the DNA double helix with high affinity but low specificity while the POU-specific domain (POUs), which is unique to POU proteins, binds to DNA with high specificity but low affinity. The POUs and POUHD domains are tethered together by a poorly conserved linker and together these domains confer high specificity and high-affinity DNA binding to sites in gene promoters. POUHD POU homeodomain, POUS POU-specific domain. B Schematic diagram showing the genomic organisation of the Brn-3b locus on human chromosome 4 (mouse chromosome 8). C Schematic diagram showing Brn-3b protein isoforms, with splicing of exons 1 and 2 giving rise to the longer Brn-3b(l) while the shorter Brn-3b(s) protein is encoded by exon 2 and therefore contains the POU domain but lacks the amino-terminal transactivation domain (TAD) found in the Brn-3b (l). Approximate sizes of the proteins are indicated. TIS transcription initiation site, TAD transactivation domain, N’ = amino terminal, C’ carboxy terminal.