Identification of a minimal promoter sequence for the human N-acetyltransferase Type I gene that binds AP-1 (activator protein 1) and YY-1 (Yin and Yang 1)

Butcher, NJ, Arulpragasam, A, Pope, C and Minchin, RF (2003) Identification of a minimal promoter sequence for the human N-acetyltransferase Type I gene that binds AP-1 (activator protein 1) and YY-1 (Yin and Yang 1). Biochemical Journal, 376 441-448. doi:10.1042/BJ20030650


Author Butcher, NJ
Arulpragasam, A
Pope, C
Minchin, RF
Title Identification of a minimal promoter sequence for the human N-acetyltransferase Type I gene that binds AP-1 (activator protein 1) and YY-1 (Yin and Yang 1)
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 2003-01-01
Year available 2003
Sub-type Article (original research)
DOI 10.1042/BJ20030650
Open Access Status Not yet assessed
Volume 376
Start page 441
End page 448
Total pages 8
Place of publication London
Publisher Portland Press
Language eng
Abstract Human N-acetyltransferase Type I (NAT1) catalyses the acetylation of many aromatic amine and hydrazine compounds and it has been implicated in the catabolism of folic acid. The enzyme is widely expressed in the body, although there are considerable differences in the level of activity between tissues. A search of the mRNA databases revealed the presence of several NAT1 transcripts in human tissue that appear to be derived from different promoters. Because little is known about NAT1 gene regulation, the present study was undertaken to characterize one of the putative promoter sequences of the NAT1 gene located just upstream of the coding region. We show with reverse-transcriptase PCR that mRNA transcribed from this promoter (Promoter 1) is present in a variety of human cell-lines, but not in quiescent peripheral blood mononuclear cells. Using deletion mutant constructs, we identified a 20 bp sequence located 245 bases upstream of the translation start site which was sufficient for basal NAT1 expression. It comprised an AP-1 (activator protein 1)-binding site, flanked on either side by a TCATT motif. Mutational analysis showed that the AP-1 site and the 3' TCATT sequence were necessary for gene expression, whereas the 5' TCATT appeared to attenuate promoter activity. Electromobility shift assays revealed two specific bands made up by complexes of c-Fos/Fra, c-Jun, YY-1 (Yin and Yang 1) and possibly Oct-1. PMA treatment enhanced expression from the NAT1 promoter via the AP-1-binding site. Furthermore, in peripheral blood mononuclear cells, PMA increased endogenous NAT1 activity and induced mRNA expression from Promoter I, suggesting that it is functional in vivo.
Keyword Biochemistry & Molecular Biology
N-acetyltransferase
Activator Protein 1 (ap-1)
Gene Induction
Promoter
Transcription Factor
Human Arylamine N-acetyltransferase-1
Stimulating Factor Gene
Gm-csf
Chromosomal Localization
Response Element
Nat1
Cells
Acetylation
Expression
Complex
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Tue, 14 Aug 2007, 00:01:19 EST