The RUNX complex: reaching beyond haematopoiesis into immunity

Abstract

SummaryAmong their diverse roles as transcriptional regulators during development and cell fate specification, the RUNX transcription factors are best known for the parts they play in haematopoiesis. RUNX proteins are expressed throughout all haematopoietic lineages, being necessary for the emergence of the first haematopoietic stem cells to their terminal differentiation. Although much progress has been made since their discoveries almost two decades ago, current appreciation of RUNX in haematopoiesis is largely grounded in their lineage-specifying roles. In contrast, the importance of RUNX to immunity has been mostly obscured for historic, technical and conceptual reasons. However, this paradigm is likely to shift over time, as a primary purpose of haematopoiesis is to resource the immune system. Furthermore, recent evidence suggests a role for RUNX in the innate immunity of non-haematopoietic cells. This review takes a haematopoiesis-centric approach to collate what is known of RUNX's contribution to the overall mammalian immune system and discuss their growing prominence in areas such as autoimmunity, inflammatory diseases and mucosal immunity.

The impact of perinatal nicotine exposure on fetal lung development and subsequent respiratory morbidity

“…Some of these changes at specific loci can result in tissue‐specific morbidities, such as an increased risk of asthma (Haley et al, ; Morales et al, ). Specific genes in cord blood studies that may play a role in childhood respiratory morbidities include AHRR, GF1, FOXP3, CYP1A1, and RUNX (Haley et al, ; Hinz et al, ; Joubert et al, ; Lee, Kwon, Lai, & Jung, ; Suter et al, ; Voon, Hor, & Ito, ). Interestingly, RUNX transcription factors play a critical role in lung development (Lee et al, ; Voon et al, .…”

“…Specific genes in cord blood studies that may play a role in childhood respiratory morbidities include AHRR, GF1, FOXP3, CYP1A1, and RUNX (Haley et al, 2011;Hinz et al, 2012;Joubert et al, 2012;Lee, Kwon, Lai, & Jung, 2014;Suter et al, 2010;Voon, Hor, & Ito, 2015). Interestingly, RUNX transcription factors play a critical role in lung development Voon et al, 2015. Airway hyperresponsiveness and asthma have been directly linked to RUNX1 polymorphisms.…”

Evolutionary Paradigms from Ancient and Ongoing Conflicts between the Lentiviral Vif Protein and Mammalian APOBEC3 Enzymes

“…CBF-β normally heterodimerizes with RUNX transcription factors to regulate gene expression programs during the development of T lymphocytes (RUNX1 and RUNX3) and bone cells (RUNX2) [15]. Crystal structures of Vif/CBF-β and RUNX1/CBF-β indicate that the two complexes are mutually exclusive and suggest that competition occurs between viral Vif and cellular RUNX proteins for the same CBF-β binding surface (Fig 1B).…”

Transcriptional control of natural killer cell differentiation

“…Members of the Runx family of TFs play prominent roles in hematopoiesis . Runx TFs share a conserved Runt domain that mediates heterodimerization with the non‐DNA binding cofactor, core‐binding factor‐ β (CBF‐ β ).…”

“…Members of the Runx family of TFs play prominent roles in hematopoiesis. 56,57 Runx TFs share a conserved Runt domain that mediates heterodimerization with the non-DNA binding cofactor, core-binding factor-b (CBFb). Heterodimerization with CBF-b is essential for the function of Runx TFs, as it increases the affinity of Runx TFs for DNA and facilitates the recruitment of coactivators and corepressors that regulate transcription by remodeling the chromatin landscape at target loci.…”