ZFIN ID: ZDB-PUB-190719-3
Hoxa2 selectively enhances Meis binding to change a branchial arch ground state
Amin, S., Donaldson, I.J., Zannino, D.A., Hensman, J., Rattray, M., Losa, M., Spitz, F., Ladam, F., Sagerström, C., Bobola, N.
Date: 2015
Source: Developmental Cell   32: 265-77 (Journal)
Registered Authors: Sagerström, Charles, Zannino, Denise
Keywords: none
MeSH Terms:
  • Animals
  • Branchial Region/metabolism*
  • Cell Line
  • Gene Expression Regulation, Developmental/physiology*
  • Homeodomain Proteins/metabolism*
  • Mice
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins/metabolism
  • Transcription Factors/metabolism
PubMed: 25640223 Full text @ Dev. Cell
Hox transcription factors (TFs) are essential for vertebrate development, but how these evolutionary conserved proteins function in vivo remains unclear. Because Hox proteins have notoriously low binding specificity, they are believed to bind with cofactors, mainly homeodomain TFs Pbx and Meis, to select their specific targets. We mapped binding of Meis, Pbx, and Hoxa2 in the branchial arches, a series of segments in the developing vertebrate head. Meis occupancy is largely similar in Hox-positive and -negative arches. Hoxa2, which specifies second arch (IIBA) identity, recognizes a subset of Meis prebound sites that contain Hox motifs. Importantly, at these sites Meis binding is strongly increased. This enhanced Meis binding coincides with active enhancers, which are linked to genes highly expressed in the IIBA and regulated by Hoxa2. These findings show that Hoxa2 operates as a tissue-specific cofactor, enhancing Meis binding to specific sites that provide the IIBA with its anatomical identity.