This protein is a member of the RUNX family of transcription factors and has a Runt DNA-binding domain. It is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Transcript variants of the gene that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing.1
Differences in RUNX2 are hypothesized to be the cause of the skeletal differences between modern humans and early humans such as Neanderthals. These differences include a different shape of the skull, a bell-shaped chest in Neanderthals, etc.2
The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased residence of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells.3
Runx proteins represent the alpha DNA binding subunit of a heteromeric protein complex that also includes the non-DNA binding beta-subunit which increases the DNA binding affinity of the alpha subunit. In addition, there is a large cohort of regulatory proteins that bind to the C-terminus of Runx2 to modify its transcriptional function. 4
^Pockwinse SM, Kota KP, Quaresma AJ, et al. (May 2011). "Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression". Journal of Cellular Physiology227 (1): 710–22. doi:10.1002/jcp.22465. PMID20945391.
^Lian, JB; Javed, A, Zaidi, SK, Lengner, C, Montecino, M, van Wijnen, AJ, Stein, JL, Stein, GS (2004). "Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors.". Critical reviews in eukaryotic gene expression14 (1-2): 1–41. PMID15104525.
^ abHess J, Porte D, Munz C, Angel P (June 2001). "AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element". J. Biol. Chem.276 (23): 20029–38. doi:10.1074/jbc.M010601200. PMID11274169.
^ abD'Alonzo RC, Selvamurugan N, Karsenty G, Partridge NC (January 2002). "Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation". J. Biol. Chem.277 (1): 816–22. doi:10.1074/jbc.M107082200. PMID11641401.
^Schroeder TM, Kahler RA, Li X, Westendorf JJ (October 2004). "Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation". J. Biol. Chem.279 (40): 41998–2007. doi:10.1074/jbc.M403702200. PMID15292260.
^Pelletier N, Champagne N, Stifani S, Yang XJ (April 2002). "MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2". Oncogene21 (17): 2729–40. doi:10.1038/sj.onc.1205367. PMID11965546.
^ abHanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K, Ito Y (October 1999). "Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter". J. Biol. Chem.274 (44): 31577–82. doi:10.1074/jbc.274.44.31577. PMID10531362.
Otto F, Kanegane H, Mundlos S (2002). "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia.". Hum. Mutat.19 (3): 209–16. doi:10.1002/humu.10043. PMID11857736.
Komori T (2002). "[Cbfa1/Runx2, an essential transcription factor for the regulation of osteoblast differentiation]". Nippon Rinsho. 60 Suppl 3: 91–7. PMID11979975.
Stock M, Otto F (2005). "Control of RUNX2 isoform expression: the role of promoters and enhancers.". J. Cell. Biochem.95 (3): 506–17. doi:10.1002/jcb.20471. PMID15838892.
Blyth K, Cameron ER, Neil JC (2005). "The RUNX genes: gain or loss of function in cancer.". Nat. Rev. Cancer5 (5): 376–87. doi:10.1038/nrc1607. PMID15864279.
Schroeder TM, Jensen ED, Westendorf JJ (2005). "Runx2: a master organizer of gene transcription in developing and maturing osteoblasts.". Birth Defects Res. C Embryo Today75 (3): 213–25. doi:10.1002/bdrc.20043. PMID16187316.
Frenkel B, Hong A, Baniwal SK, Coetzee GA, Ohlsson C, Khalid O, Gabet Y (August 2010). "Regulation of adult bone turnover by sex steroids". J. Cell. Physiol.224 (2): 305–10. doi:10.1002/jcp.22159. PMID20432458.