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Dev Cell. 2015 Feb 9;32(3):265-77. doi: 10.1016/j.devcel.2014.12.024. Epub 2015 Jan 29.

Hoxa2 selectively enhances Meis binding to change a branchial arch ground state.

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School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, USA.
Department of Computer Science, University of Sheffield, Sheffield S1 4DP, UK; The Sheffield Institute for Translational Neuroscience, Sheffield S10 2HQ, UK.
Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK; Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK. Electronic address:


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.

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