RUNX proteins are a family of “runt-related transcription factors” encoded by three different genes in mammals: RUNX1, RUNX2, and RUNX3. They are considered master regulators of embryonic development. These proteins control how other genes are utilized, influencing cell proliferation, differentiation, and lineage determination.
The Role of a Master Gene Regulator
RUNX proteins function as master regulators by binding directly to specific DNA sequences within genes. This binding typically occurs at a core consensus sequence through a specialized part of the protein called the runt domain. To increase their binding affinity and stability, RUNX proteins form a complex with a partner protein known as Core-Binding Factor beta (CBFβ). This partnership allows the RUNX complex to control processes like cellular differentiation and cell cycle progression.
Essential Functions in Development
RUNX proteins have important roles during development, particularly in forming specialized tissues. RUNX1 is recognized for its important role in hematopoiesis, the process of generating all types of blood cells. This includes guiding the differentiation of various lineages into mature blood components. RUNX2 acts as a primary regulator of osteogenesis, the formation and development of bone, directing the expression of genes necessary for building bone tissue. Beyond these roles, RUNX proteins also contribute to the development of nerve cells and hair follicles.
Connection to Human Health
Dysfunction in RUNX genes or their proteins can lead to health conditions. Mutations in the RUNX1 gene are linked to various hematological malignancies, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Inherited mutations in RUNX1 can cause Familial Platelet Disorder with predisposition to acute myeloid leukemia (FPD/AML). Acquired somatic mutations in RUNX1 are also found in sporadic cases of AML, where they can contribute to a poorer prognosis.
Defects in the RUNX2 gene cause cleidocranial dysplasia, an autosomal dominant disorder affecting bone and tooth development. Individuals with this condition often exhibit characteristic features such as delayed closure of the soft spots on the skull (fontanels), underdeveloped or absent collarbones (hypoplastic clavicles), and various dental issues, including the presence of extra teeth. Understanding how these RUNX gene alterations disrupt normal development provides scientists with insights into the molecular basis of these diseases, paving the way for potential diagnostic and therapeutic strategies.