Background information
Hox, Pbx and Meis families of transcription factors form heteromeric complexes and bind DNA through specific homeobox domains. Hox proteins are involved in regulating tissue patterning during development, and are also expressed in lineage- and stage-specific patterns during adult hematopoietic differentiation and in leukemias. The Hox proteins, which include paralog groups 1-10, have a low intrinsic binding affinity for DNA and are instead associated into cooperative DNA binding complexes with Pbx or the Pbx- related Meis proteins, which result in an enhanced Hox-DNA binding affinity and an increased selectivity for the binding site. Both Meis1 and Meis2 (also known as Meis-related gene 1 or Mrg1) are members of the TALE (“three amino acid loop extensionâ€) family of homeodomain-containing proteins. In addition to binding with Hox proteins, Meis1 also forms heterodimers with the ubiquitously expressed Pbx proteins, including Pbx1, Pbx2 and Pbx3, and these complexes contain distinct DNA-binding specificities. Like Hox and Pbx proteins, Meis1 is implicated in oncogenesis, as it is overexpressed as a result of adjacent retroviral insertion in BHX-2 myeloid leukemias. Two Meis-related proteins, Meis2 and Meis3 (also designated Mrg1 and Mrg2, respectively), possess largely similar sequence identity with Meis1 and are expressed in normal tissues and myeloid leukemias. In the pancreas, Meis2 preferentially associates with Pbx1, and together they associate with the pancreas-specific homeodomain factor, Pdx1, to repress Pdx1-induced transcriptional activation.
