title: Hoxa2 selectively enhances Meis binding to change a branchial arch ground state.
abstract: 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.
authors: School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Shilu
authors: S
authors: Amin
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Ian J
authors: IJ
authors: Donaldson
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, USA.
authors: Denise A
authors: DA
authors: Zannino
authors: Department of Computer Science, University of Sheffield, Sheffield S1 4DP, UK; The Sheffield Institute for Translational Neuroscience, Sheffield S10 2HQ, UK.
authors: James
authors: J
authors: Hensman
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Magnus
authors: M
authors: Rattray
authors: School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Marta
authors: M
authors: Losa
authors: Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors: François
authors: F
authors: Spitz
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, USA.
authors: Franck
authors: F
authors: Ladam
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, USA.
authors: Charles
authors: C
authors: Sagerström
authors: 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: nicoletta.bobola@manchester.ac.uk.
authors: Nicoletta
authors: N
authors: Bobola
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000378:metabolism*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; C102641:Mrg1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors
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