title: The PBX-regulating protein PREP1 is present in different PBX-complexed forms in mouse.
abstract: Human PREP1, a novel homeodomain protein of the TALE super-family, forms a stable DNA-binding complex with PBX proteins in solution, a ternary complex with PBX and HOXB1 on DNA, and is able to act as a co-activator in the transcription of PBX-HOXB1 activated promoters (Berthelsen, J., Zappavigna, V., Ferretti, E., Mavilio, F., Blasi, F. , 1998b. The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperatity. EMBO J. 17, 1434-1445; Berthelsen, J., Zappavigna, V., Mavilio, F., Blasi, F., 1998c. Prep1, a novel functional partner of Pbx proteins. EMBO J. 17, 1423-1433). Here we demonstrate the presence of DNA-binding PREP1-PBX complexes also in murine cells. In vivo, PREP1 is a predominant partner of PBX proteins in various murine tissues. However, the choice of PBX family member associated with PREP1 is largely tissue-type specific. We report the cloning and expression domain of murine Prep1 gene. Murine PREP1 shares 100% identity with human PREP1 in the homeodomain and 95% similarity throughout the whole protein. In the adult mouse, PREP1 is expressed ubiquitously, with peaks in testis and thymus. We further demonstrate the presence of murine Prep1 mRNA and protein, and of different DNA-binding PREP1-PBX complexes, in mouse embryos from at least 9.5 days p.c. Moreover, we show that PREP1 is present in all embryonic tissues from at least 7.5-17.5 days p.c with a predominantly nuclear staining. PREP1 is able to super-activate the PBX-HOXB-1 autoregulated Hoxb-1 promoter, and we show that all three proteins, PREP1, PBX and HOXB-1, are present together in the mouse rhombomere 4 domain in vivo, compatible with a role of PREP1 as a regulator of PBX and HOXB-1 proteins activity during development.
authors.affiliation: Molecular Genetics Unit, Department of Biology and Biotechnology (DIBIT), H.S. San Raffaele Scientific Institute, via Olgettina 58, 20132, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferretti
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: D
authors.initials: D
authors.lastname: Talarico
authors.forename: F
authors.initials: F
authors.lastname: Blasi
authors.forename: J
authors.initials: J
authors.lastname: Berthelsen
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C106682:PKNOX1 protein, human; C491412:Pknox1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human