Transcriptional Regulation of the Human TATA Binding Protein Gene

• Published in: Genomics (San Diego, Calif.) Calif.), 2002-04, Vol.79 (4), p.479-482
• Main Authors: Harland, Lee, Crombie, Robert, Anson, Simon, deBoer, Jasper, Ioannou, Panayiotis A., Antoniou, Michael
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 6 - genetics; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Gene Silencing; Genome, Human; Humans; Molecular and cellular biology; Molecular genetics; PDCD2 gene; Promoter Regions, Genetic; PSMB1 gene; Sequence Analysis, DNA; TATA-Box Binding Protein; TBP gene; Transcription Factors - genetics; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transgenes
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2002.6728

The human TATA binding protein (TBP) locus consists of a functional domain of three closely linkedhousekeeping genes (TBP, PSMB1 (proteasomal C5 subunit), and PDCD2 (programmed cell death-2)) within a 50-kb interval at chromosome position 6q27. Here we demonstrate that a genomic clone spanning the 20-kb TBP gene, with 12 kb 5′ and 3′ flanking sequences, was fully functional in stable, transfected L-cells harboring a single copy of this transgene, including after long-term (60 day) culture in the absence of drug selective pressure. Furthermore, we were only able to detect DNaseI hypersensitive sites at the TBP and PSMB1 promoters present within this 44-kb fragment. Our data suggest that this 44-kb genomic region possesses genetic regulatory elements that not only drive ubiquitous expression of TBP but also negate chromatin and DNA methylation induced silencing, which is normally associated with transgenes stably integrated into tissue culture cells.