Primary Structure, Neural-specific Expression, and Chromosomal Localization of Cux-2, a Second Murine Homeobox Gene Related to Drosophila cut*
- From the ‡ Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 and
- ¶ Department of Biology, University of Michigan, Ann Arbor, Michigan 48109
- ∥ An Established Investigator of the American Heart Association, to whom correspondence and reprint requests should be addressed: Nephrology Section, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. Tel.: 203-785-4185; Fax: 203-785-7068; E-mail: peter.igarashi{at}yale.edu.
Abstract
The cut locus of Drosophila encodes a diverged homeodomain-containing protein that is required for the development of external sensory (es) organs and other tissues. A homologous gene (Cux-1) that encodes a transcriptional repressor has been identified in the mouse and other mammals. We have identified a second murine homeobox-containing gene (designated Cux-2) that is structurally related to Drosophila cut. The murine Cux-2 homeobox was similar to Drosophila cut and encoded a homeodomain that contained a characteristic histidine residue at position 50. The predicted Cux-2 protein contained 1426 amino acids and included three internal 60-amino acid repeats (Cut repeats) that were previously found in Drosophila Cut and murine Cux-1. Unlike Cux-1, expression of Cux-2 was restricted to neural tissue. In the adult brain, Cux-2 was prominently expressed in neurons in the thalamus and limbic system. In embryos, Cux-2 was expressed in the developing central and peripheral nervous systems, including the telencephalon and peripheral ganglia of the trigeminal and glossopharyngeal nerves. A glutathione S-transferase fusion protein containing the carboxyl-terminal Cut repeat and homeodomain of Cux-2 exhibited sequence-specific binding to oligonucleotides derived from the promoter of the Ncam gene. Using an interspecific backcross panel, Cux-1 and Cux-2 were mapped to distinct loci that were genetically linked on distal chromosome 5. These results demonstrate that a family of homeobox genes related to Drosophila cut is located on chromosome 5 in the mouse. Cux-2 is expressed exclusively in the central and peripheral nervous systems, and the Cux-2 gene product binds to DNA in a sequence-specific manner. Cux-2 may encode a transcription factor that is involved in neural specification in mammals.
Footnotes
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↵§ Recipient of a Clinician-Scientist Award from the Medical Research Council of Canada.
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↵* This work was supported by United States Public Health Service Research Grants RO1 DK-45678 (to P. I.) and RO1 NS-29119 (to R. B.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- bp
-
base pair(s)
- kb
-
kilobase pair(s)
- d.p.c.
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days post coitus
- EMSA
-
electrophoretic mobility-shift assays
- CDP
-
CCAAT displacement protein
- GST
-
glutathione S-transferase
- GAPDH
-
glyceraldehyde-3-phosphate dehydrogenase
- RFLP
-
restriction fragment length polymorphism
- ISH
-
in situ hybridization
- PCR
-
polymerase chain reaction.
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↵2The murine cut homologue previously cloned by Valarché et al. (13) was named Cux in accordance with the nomenclature recommendations of Scott. Because our studies reveal the existence of at least two murine cut homologues, we refer to the homologue cloned by Valarché et al. as Cux-1. Cux-2 refers to the second cut homologue reported herein. The corresponding gene symbols assigned by the International Committee on Standardized Nomenclature for Mice are Cutl1 and Cutl2, respectively.
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↵3The nucleotide and amino acid sequences described in this report have been deposited in the GenBank™ data base (accession no. U45665[GenBank]).
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- Received November 30, 1995.
- Revision received May 31, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
