Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7549
Analysis of the DNA-binding profile and function of TALE homeoproteins reveals their specialization and specific interactions with Hox genes/proteins
Penkov, Dmitry | Mateos San Martín, Daniel | Fernandez-Díaz, Luis C | Rossello, Catalina A CNIC | Torroja, Carlos CNIC | Sanchez-Cabo, Fatima CNIC | Warnatz, H J | Sultan, Marc | Yaspo, Marie L | Gabrieli, Arianna | Tkachuk, Vsevolod | Brendolan, Andrea | Blasi, Francesco | Torres, Miguel CNIC
Cell Rep. 2013; 3(4):1321-33
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.
Animals | Binding Sites | DNA | Embryo, Mammalian | Genome | Homeodomain Proteins | Mice | Myeloid Ecotropic Viral Integration Site 1 Protein | Neoplasm Proteins | Pre-B-Cell Leukemia Transcription Factor 1 | Promoter Regions, Genetic | Protein Binding | Thymocytes | Transcription Factors | Transcription Initiation Site
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