Upstream and downstream targets of RUNX proteins

In recent years, the in vivo role of the three members of the RUNX family of transcription factors has in part been elucidated. While Runx1 is essential for mature haematopoiesis and Runx2 for osteochondrogenesis, Runx3 has a function in the nervous system. Translocations and mutations affecting the RUNX1 gene are clearly implicated in leukemogenesis whereas recent data suggest that changed expression levels of RUNX3 may be involved in gastric carcinogenesis. Germ line mutations in RUNX2 have been identified in patients with an autosomal dominant skeletal disorder, cleidocranial dysplasia. While a number of pathways have been delineated that regulate RUNX activity, transcription factors binding to RUNX promoters are only beginning to be identified. A growing number of genes have been characterised that are being regulated in their transcriptional activity by different RUNX proteins. Whether a particular RUNX protein specifically targets a defined subset of downstream genes or whether there is some redundancy as to which RUNX protein activates which target promoter remains to be elucidated.