Perspectives on RUNX genes: an update.
This perspective on RUNX genes discusses their basic biological features, including their DNA-binding alpha subunit, their non-DNA binding beta subunit, and their Runt domain. The evolution of Runx genes begins with one most like Runx3 in invertebrates, progresses to four genes in Drosophila, and to three in vertebrates. Runx genes have two promoters and various numbers of exons and isoforms. All three genes with expressions in the same biological tissues act either synergistically or at different time periods. Runx genes have downstream target genes. Furthermore, Runx genes are mediated by TGFbeta or BMP pathways. They also have cohesin-dependent regulation. Runx1 binds the CD4 silencer and represses transcription in immature double negative thymocytes. Runx1 also activates CD8 as the double negative population progresses to double positive thymocytes. Runx3 establishes epigenetic silencing in CD4 - CD8+ cytotoxic T-cells by binding the CD4 silencer core sequence. Runx1 may also be involved in CD4 silencing in CD8+ T-cells. RUNX1 mutations cause familial thrombocytopenia with a propensity for developing acute myelogenous leukemia; two functional consequences of these mutations include haploinsufficiency and a dominant negative effect. The latter tends to be associated with a higher frequency of leukemia. RUNX2 mutations cause cleidocranial dysplasia; most are of the missense type and commonly occur in the Runt domain. RUNX3 is a tumor suppressor gene with hemizygous deletion of one allele and hypermethylation of the other, resulting in gastric adenocarcinoma.
Cohen
M Michael
MM
Department of Pediatrics, Faculty of Medicine, Dalhousie University, 5981 University Avenue, Halifax, Nova Scotia, Canada B3H 1W2. mmichael.cohenjr@gmail.com
D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D004194:Disease / Q000235:genetics; D019143:Evolution, Molecular; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007107:Immune System / Q000378:metabolism; D009154:Mutation / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit