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Nucleic Acids Research, 2002, Vol. 30, No. 9 2043-2051
© 2002 Oxford University Press

Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors

C. Fognani, C. Kilstrup-Nielsen1, J. Berthelsen, E. Ferretti, V. Zappavigna1 and F. Blasi*

Unit of Molecular Genetics and 1Unit of Transcriptional Regulation of Development, DIBIT, Department of Molecular Biology and Functional Genetics, Università Vita Salute San Raffaele, Via Olgettina 58, 20132 Milano, Italy

TALE (three amino acid loop extension) homeodomain proteins include the PBC and the MEINOX sub-families. MEINOX proteins form heterodimer complexes with PBC proteins. Heterodimerization is crucial to DNA binding and for nuclear localization. PBC–MEINOX heterodimers bind DNA also in combination with HOX proteins, thereby modulating their DNA-binding specificity. TALE proteins therefore play crucial roles in multiple developmental and differentiation pathways in vivo. We report the identification and characterization of a novel human gene homologous to PREP1, called PREP2. Sequence comparisons indicate that PREP1 and PREP2 define a novel sub-family of MEINOX proteins, distinct from the MEIS sub-family. PREP2 is expressed in a variety of human adult tissues and displays a more restricted expression pattern than PREP1. PREP2 is capable of heterodimerizing with PBC proteins. Heterodimerization with PBX1 appears to be essential for nuclear localization of both PREP2 and PBX1. A comparison between the functional properties of PREP1 and PREP2 reveals that PREP2–PBX display a faster DNA-dissociation rate than PREP1–PBX heterodimers, suggesting different roles in controlling gene expression. Like PREP1, PREP2–PBX heterodimers are capable of forming ternary complexes with HOXB1. The analysis of some PREP2 in vitro properties suggests a functional diversification among PREP and between PREP and MEIS MEINOX proteins.

* To whom correspondence should be addressed. Tel: +39 02 2643 4832; Fax: +39 02 2643 4844; Email: blasi.francesco{at}hsr.it Present addresses:C. Fognani, Department of Biology, University of Milan, Via Celoria 26, 20133 Milan, Italy J. Berthelsen, Pharmacia, Viale Pasteur 10, 20014 Nerviano, Milano, Italy


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