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ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

Hélène Kiefer, Fabienne Chatail-Hermitte, Philippe Ravassard, Elisa Bayard, Isabelle Brunet, and Jacques Mallet^*

Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Hôpital de la Pitié-Salpêtrière, Paris, France

Received 14 May 2004/ Returned for modification 30 July 2004/ Accepted 18 November 2004

The rat tyrosine hydroxylase gene promoter contains an E-box/dyad motif and an octameric and heptameric element that may be recognized by classes of transcription factors highly expressed during nervous system development. In a one-hybrid genetic screen, we used these sites as targets to isolate cDNAs encoding new transcription factors present in the brain. We identified ZENON, a novel rat POZ protein that contains two clusters of Kruppel-like zinc fingers and that presents several features of a transcription factor. ZENON is found in nuclei following transient transfection with the cDNA. The N-terminal zinc finger cluster contains a DNA binding domain that interacts with the E box. Cotranfection experiments revealed that ZENON induces tyrosine hydroxylase promoter activity. Unlike other POZ proteins, the ZENON POZ domain is not required for either activation of transcription or self-association. In the embryonic neural tube, ZENON expression is restricted to neurons that have already achieved mitosis and are engaged in late stages of neuronal differentiation (late postmitotic neurons). ZENON neuronal expression persists in the adult brain; therefore, ZENON can be considered a marker of mature neurons. We propose that ZENON is involved in the maintenance of panneuronal features and/or in the survival of mature neurons.

Present address: Division of Molecular Neurobiology, Department of Basic Medical Sciences, Institute of Medical Sciences, University of Tokyo, Minato-Ku, Tokyo 108-8639, Japan.

Present address: Ipsogen, Luminy Biotech Enteprise, 13009 Marseille, France.

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