title: Analysis of the DNA-binding profile and function of TALE homeoproteins reveals their specialization and specific interactions with Hox genes/proteins.
abstract: The interactions of Meis, Prep, and Pbx1 TALE homeoproteins with Hox proteins are essential for development and disease. Although Meis and Prep behave similarly in vitro, their in vivo activities remain largely unexplored. We show that Prep and Meis interact with largely independent sets of genomic sites and select different DNA-binding sequences, Prep associating mostly with promoters and housekeeping genes and Meis with promoter-remote regions and developmental genes. Hox target sequences associate strongly with Meis but not with Prep binding sites, while Pbx1 cooperates with both Prep and Meis. Accordingly, Meis1 shows strong genetic interaction with Pbx1 but not with Prep1. Meis1 and Prep1 nonetheless coregulate a subset of genes, predominantly through opposing effects. Notably, the TALE homeoprotein binding profile subdivides Hox clusters into two domains differentially regulated by Meis1 and Prep1. During evolution, Meis and Prep thus specialized their interactions but maintained significant regulatory coordination.
authors.affiliation: Foundation FIRC Institute of Molecular Oncology at the IFOM-IEO Campus, via Adamello 16, 20139 Milan, Italy.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Penkov
authors.forename: Daniel
authors.initials: D
authors.lastname: Mateos San Martín
authors.forename: Luis C
authors.initials: LC
authors.lastname: Fernandez-Díaz
authors.forename: Catalina A
authors.initials: CA
authors.lastname: Rosselló
authors.forename: Carlos
authors.initials: C
authors.lastname: Torroja
authors.forename: Fátima
authors.initials: F
authors.lastname: Sánchez-Cabo
authors.forename: H J
authors.initials: HJ
authors.lastname: Warnatz
authors.forename: Marc
authors.initials: M
authors.lastname: Sultan
authors.forename: Marie L
authors.initials: ML
authors.lastname: Yaspo
authors.forename: Arianna
authors.initials: A
authors.lastname: Gabrieli
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Tkachuk
authors.forename: Andrea
authors.initials: A
authors.lastname: Brendolan
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
mesh_terms: D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D016678:Genome; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060168:Thymocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C481797:Pbx1 protein, mouse; C491412:Pknox1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors; D004247:DNA