CLONING, CHARACTERIZATION, AND CHROMOSOMAL ASSIGNMENT OF THE HUMAN ORTHOLOG OF MURINE ZFP-37, A CANDIDATE GENE FOR NAGER-SYNDROME

In an effort to identify putative transcription factors involved in ch ondrocyte differentiation during human endochondral bone formation, a human fetal cartilage-specific cDNA library was screened with a degene rate oligonucleotide probe corresponding to a conserved stretch of eig ht amino acids from the zinc finger region of the Drosophila Kruppel g ene family of DNA-binding proteins. Using this strategy, we have ident ified a novel zinc finger gene ZFP-37. ZFP-37 corresponds to a putativ e transcription factor containing 12 tandemly repeated zinc finger mot ifs and a Kruppel-associated box (KRAB) domain. The KRAB domain has be en reported to function as a transcriptional repressor and is located in the amino terminus, while the zinc finger repeats are positioned at the carboxy-terminal end of ZFP-37. Gene mapping with a somatic cell hybrid panel and fluorescence in situ hybridization (FISH) localized Z FP-37 to human Chr 9q32. The gene is expressed at low level as a 3.2-k b mRNA in several tissues including fetal human cartilage. Sequence co mparison revealed that ZFP-37 may represent the human homolog of the m ouse gene Zfp-37. The map location and expression pattern suggest ZFP- 37 as a candidate gene for a craniofacial-limb malformation, Nager syn drome (acrofacial dysostosis).