[8] It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα).

As a transcription factor (TF), its DNA binding ability is encoded by the runt domain (residues 50 – 177), which is homologous to the p53 family.

The runt domain of RUNX1 binds to the core consensus sequence TGTGGNNN (where NNN can represent either TTT or TCA).

[12] Nusslein-Volhard and Wieschaus discovered the transcription factor RUNX in a screen that was conducted to identify mutations that affect segment number and polarity in Drosophila.

[14] Subsequently, in 1991, Ohki et al. cloned the human RUNX1 gene; RUNX1 was found to be rearranged in the leukemic cell DNAs from t(8;21)(q22;q22) AML patients.

Runx1 was purified as a sequence-specific DNA-binding protein that regulated the disease specificity of the Moloney murine Leukemia virus.

[20] Similar experiments from a different research group demonstrated that the knockout embryos die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS).

It is expressed in all haematopoietic sites that contribute to the formation of haematopoietic stem and progenitor cells (HSPCs), including the yolk sac,[22] allantois, placenta, para-aortic splanchnopleura (P-Sp; (the visceral mesodermal layer),[23] aorta-gonad-mesonephros (AGM) and the umbilical and vitelline arteries.

[27] This +23 RUNX1 enhancer contains conserved motifs that encourage binding of various haematopoiesis related regulators such as Gata2, ETS factors (Fli-1, Elf-1, PU.1) and the SCL / Lmo2 / Ldb1 complex, as well as RUNX1 itself acting in an auto-regulatory loop.

Examples range from RUNX1 point mutations acquired from low-dose radiation leading to myelodysplastic neoplasms or therapy-related myeloid neoplasms, to chromosomal translocation of the RUNX1 gene with the ETO / MTG8 / RUNX1T1 gene located on chromosome 8q22, t(8; 21), generating a fusion protein AML-ETO, categorized as acute myeloid leukemia (AML) M2.

As a consequence, AML-ETO retains the ability to bind at RUNX1 target genes whilst acting as a transcription repressor via the recruitment of corepressors and histone deacetylases, which is an intrinsic function of ETO.

A key factor in apoptosis initiation is the protein NOXA, which is suppressed in a particularly aggressive form of pancreatic cancer.

Pharmacological or genetic inhibition of RUNX1 de-represses the NOXA gene and induces apoptosis in pancreatic cancer cells.