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.
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.
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.
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. 
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