Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding regulatory proteins differentially expressed during development.
We report the isolation of a cDNA encoding a mammalian homeoprotein related to the Drosophila cut gene product, called Clox, for Cut like homeobox. In addition to the homeodomain, three 73-amino acid repeats, the so-called cut repeats, are also conserved between Cut and the mammalian counterpart described here. This conservation suggests that the cut repeat motif may define a new class of homeoproteins. Both cloned and endogenous Clox proteins are nuclear DNA-binding proteins with very similar sequence specificity. Western blot analysis revealed several distinct Clox protein species in a variety of tissues and cell types. The relative abundance of these proteins is regulated during mouse development and cell differentiation in culture. Interestingly, approximately 180-190 x 10(3) M(r) Clox proteins predominate in early embryos and are upregulated in committed myoblasts and chondrocytes, but downregulated upon terminal differentiation. Clox DNA-binding activity is correlated with the abundance of these proteins. In contrast, larger Clox protein species (approximately 230-250 x 10(3) M(r)) are detected mainly in adult tissues and in terminally differentiated cells. Cotransfection experiments show that Clox proteins can function as repressors of tissue-specific gene transcription. Thus, Clox, like their Drosophila counterparts, are candidate regulators of cell-fate specification in diverse differentiation programs.
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts.
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Andres
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Nadal-Ginard
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Mahdavi
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data
D004268:DNA-Binding Proteins