Primary and secondary hypertriglyceridemia is common in the general population, but the biochemical basis for this disease is largely unknown. With the use of transgenic technology, two lines of mice were created that express the human apolipoprotein CIII gene. One of these mouse lines with 100 copies of the gene was found to express large amounts of the protein and to be severely hypertriglyceridemic. The other mouse line with one to two copies of the gene expressed low amounts of the protein, but nevertheless manifested mild hypertriglyceridemia. Thus, overexpression of apolipoprotein CIII can be a primary cause of hypertriglyceridemia in vivo and may provide one possible etiology for this common disorder in humans.

We report here a detailed study of developmental changes in the methylation status of specific sites In a siije-opy tissue-specific gene, from the germ ceil thropg the early embryo to adult tissues.

We constructed deletion-substitution and linker-scanning mutations in the 5'-flanking region of the Drosophila melanogaster 5S RNA gene. In vitro transcription of these templates in Drosophila and HeLa cell extracts revealed the presence of an essential control region (-30 region) located between nucleotides -39 and -26 upstream of the transcription initiation site: deletion of sequences upstream of nucleotide position -39 had no detectable effect on the wild-type level of in vitro transcription, whereas mutations extending between positions -39 and 1 resulted in templates with decreased transcriptional levels; specifically, deletion and linker-scanning mutations in the -34 to -26 region (-30 region) resulted in loss of transcription. The -30 region is essential for transcription and therefore forms part of the Drosophila 5S RNA gene transcription promoter. Compared with the activity of the wild-type gene, mutant 5S DNAs exhibited no impairment in the ability to sequester limiting transcription factors in a template exclusion competition assay. While we do not know which transcription factor(s) interacts with the -30 region, the possible involvement of RNA polymerase Ill at this region is discussed.Transcription of genes by RNA polymerase III is controlled by sequences within the region encoding the RNA. As first proposed by Sakonju et al. (17), these regions were defined as "control regions" rather than as "promoters," because evidence was not available that RNA polymerase III recognizes and binds to these sequences. Xenopus laevis 5S RNA gene transcription requires three transcription factor activities (TFIIIA, TFIIIB, and TFIIIC) as well as RNA polymerase III (19). TFIIIA is a positive transcription factor that binds to the defined internal control region (5, 23). The interaction of TFIIIC, TFIIIA, and SS DNA forms a stable complex, referred to as stable complex I, directed by the internal control region which is sequestered into the stable transcription complex by interaction with TFIIIB (1). The current model for class III gene transcription is that RNA polymerase III recognizes this stable complex and initiates transcription (1,3,20). Since the recognition sequences for transcription factors are downstream from the site of initiation, it is conceivable that RNA polymerase III itself interacts in the 5'-flanking region of 5S DNA.Transposon-directed (Tn9) deletion mutants of X. laevis 5S DNA failed to reveal essential control sequences upstream of the 49-nucleotide nonrepetitive sequence immediately adjacent to the 5' terminus of the gene (6). Furthermore, extensive computer analysis of sequences preceding several 5S RNA genes revealed several common features (9) the deletion of which, while reducing transcription, did not result in loss of transcription (17). The transcription efficiency of Bombyx mori 5S DNA was, however, reduced to 5% of the level of wild-type transcription upon deletion of the sequence upstream to coordinate -17 (14). This critical region was shown to have a sequence similar to the 5'-fl...

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