Hox cofactors in vertebrate development

Abstract

Hox genes encode homeodomain-containing transcription factors that pattern the body axes of animal embryos. It is well established that the exquisite DNA-binding specificity that allows different Hox proteins to specify distinct structures along the body axis is frequently dependent on interactions with other DNA-binding proteins which act as Hox cofactors. These include the PBC and MEIS classes of TALE (Three Amino acid Loop Extension) homeodomain proteins. The PBC class comprises fly Extradenticle (Exd) and vertebrate Pbx homeoproteins, whereas the MEIS class includes fly Homothorax (Hth) and vertebrate Meis and Prep homeoproteins. Exd was first implicated as a Hox cofactor based on mutant phenotypes in the fly. In vertebrates, PBC and MEIS homeobox proteins play important roles in development and disease. In this review, we describe the evidence that these functions reflect a requirement for Pbx and Meis/Prep proteins as Hox cofactors. However, there is mounting evidence that, like in the fly, Pbx and Meis/Prep proteins function more broadly, and we also discuss how "Hox cofactors" function as partners for other, non-Hox transcription factors during development. Conversely, we review the evidence that Hox proteins have functions that are independent of Pbx and Meis/Prep cofactors and discuss the possibility that other proteins may participate in the DNA-bound Hox complex, contributing to DNA-binding specificity in the absence of, or in addition to, Pbx and Meis/Prep.

Hox genes in hematopoiesis and leukemogenesis

“…HOX cofactors of the threeamino acid loop extension class have been shown to interact directly with HOX proteins to increase their DNA-binding affinity and specificity and to modify their transregulatory properties (Moens and Selleri, 2006). In general, HOX proteins from paralog groups 1-10 interact physically with PBX1, while those from paralog groups 9-13 interact with MEIS1 (Shen et al, 1997).…”

Rethinking the proximodistal axis of the vertebrate limb in the molecular era

“…The Meis proteins regulate the activities of the transcription factor Pbx and Hox genes (for review, see Moens and Selleri 2006). The Meis genes are more than just markers for the stylopod, as they may themselves play a role in proximal specification; since ectopic expression of these genes can reprogram proximodistal fate at least to some extent (Capdevila et al 1999;Meracader 2000).…”

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

“…We proposed to analyze cellular and molecular characteristics of human adult MSCs derived from different body locations, such as bone marrow from iliac crest (Ic-MSCs), sternum (St-MSCs) and vertebrae (vMSCs), as well as colon (Co-MSCs) and dental pulp (DPSCs). We previously investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues [15]. We observed that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures [16].…”