RUNX2

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a is_associated_with::protein that in humans is encoded by the RUNX2 is_associated_with::gene. RUNX2 is a key is_associated_with::transcription factor associated with is_associated_with::osteoblast differentiation.

Function
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 is_associated_with::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 is_associated_with::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 is_associated_with::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.

Pathology
Mutations in Cbfa1/Runx2 are associated with the disease is_associated_with::Cleidocranial dysostosis.

Co-factors
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.

Interactions
RUNX2 has been shown to interact with:


 * AR
 * ER-α
 * is_associated_with::C-Fos.
 * is_associated_with::C-jun,
 * is_associated_with::HDAC3,
 * is_associated_with::MYST4,
 * SMAD1
 * SMAD3, and
 * is_associated_with::STUB1.

miR-133 directly inhibits Runx2.