Transcriptional regulation of the human TATA binding protein gene.
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.
Harland
Lee
L
Nuclear Biology Group, Division of Medical and Molecular Genetics, GKT School of Medicine, 8(th) Floor Guy's Tower, Guy's Hospital, London Bridge, London, SE1 9RT, UK.
Crombie
Robert
R
Anson
Simon
S
deBoer
Jasper
J
Ioannou
Panayiotis A
PA
Antoniou
Michael
M
D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes
D004268:DNA-Binding Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors