ZFP-37 IS A MEMBER OF THE KRAB ZINC-FINGER GENE FAMILY AND IS EXPRESSED IN NEURONS OF THE DEVELOPING AND ADULT CNS

The murine Zfp-37 gene encodes a protein with 12 zinc fingers at its C -terminus (Nelki ct al., 1990, Nucleic Acids Res. 18: 3655; Burke and Wolgemuth, 1992, Nucleic Acids Res. 20: 2827-2834). Contrary to the pu blished data, our Northern blot analysis demonstrates not only that th e Zfp-37 gene is expressed as 2.3, 2.6, and 4.2 kb mRNAs in testis, bu t also that there is a 3.7-kb message in the adult mouse brain. Using a partial cDNA as a probe, we have isolated a brain-specific Zfp-37 cD NA clone of 3.3 kb, whose sequence was extended to full length using 5 ' end RACE. This revealed that the 3.7-kb mRNA is in fact a collection of transcripts with heterogeneous 5' ends. Comparison of cDNA and gen omic sequences shows that the Zfp-37 gene is spread over a region of s imilar to 20 kb and consists of six exons, the large 3' end exon conta ining the complete zinc finger domain, and 3' UTR. Our data show that the Zfp-37 gene utilizes different promoters, alternative splicing, an d differential polyadenylation to generate the distinct transcripts of brain and testis. Several protein isoforms are encoded by these mRNAs , some of which contain a truncated form of a conserved domain (Kruppe l-associated box) found in other zinc finger genes. In situ hybridizat ion analysis of postnatal brain sections indicates that the Zfp-37 gen e is expressed in all neurons of the central nervous system. Together, these results suggest that ZFP-37 is a transcriptional regulator pred ominantly present in postmitotic cells from two different lineages. (C ) 1996 Academic Press, Inc.