Chromosome 6 and RUNX2/RUNX2. (a) Chromosome 6 and location of RUNX2. The green bracket approximately spans the minimal common region of gain identified by array comparative genomic hybridisation (aCGH) studies of osteosarcomas, between cytobands 6p21.2 to 6p12.3 (spanning nucleotide positions 36,800,000 bp to 51,100,000 bp, resp.). All genomic information was obtained from UCSC Genome Browser (http://genome.ucsc.edu/), March 2006 (hg18) assembly. (b) Gene structure of RUNX2. Major isoforms MASNS and MRIPV are transcribed starting from promoters P1 and P2, respectively, and ATG indicates the start codon. The MRIPV isoform is encoded from exons 2–8, while the MASNS isoform is encoded from all eight exons. The Runt homology domain (RHD) is encoded from portions of exons 2, 3 and 4 (shaded). (c) Protein structure of RUNX2. The Type II/p57 isoform comprises 521 amino acids and begins with the bone-specific N-terminal MASNS polypeptide. It has a glutamine/alanine (QA) rich tract and a proline/serine/threonine (PST) rich tract that are both unique to RUNX2 in the RUNX family of proteins. The protein also possesses the RHD DNA-binding domain, the nuclear-localisation signal (NLS), the nuclear matrix targeting signal (NMTS), and the C-terminal VWRPY domain for TLE/Groucho corepressor interactions. Adapted from [44, 45, 49, 50].
