Regulation of transcription of the murine γ-glutamyl hydrolase gene. Delineation of core promoter A and the role of LYF-1, E2F and ETS-1 in determining tumor-specific expression Journal Article

  

Authors:	Masumoto, N.; Chen, J.; Sirotnak, F. M.
Article Title:	Regulation of transcription of the murine γ-glutamyl hydrolase gene. Delineation of core promoter A and the role of LYF-1, E2F and ETS-1 in determining tumor-specific expression
Abstract:	Our earlier studies (Gene 268 (2001) 183) showed that transcription of the mouse γ-glutamyl hydrolase (γGH) gene is under the control of two separate promoters widely distributed within the genome. We now report on further studies examining the functional characteristics of the more efficient promoter (promoter A) which is contiguous with an exon 1 (exon A1a) alternate within the main body of the gene. Functional deletion analysis of promoter A in pGL3 transfected in NIH3T3 cells defined a 189 bp region of sequence 26 bp upstream of exon A1a as mediating core promoter transcriptional activity. Further functional deletion analysis and site-directed mutagenesis attributed the activity of this core region to the presence of five SP1 sites within the most upstream 130 bp of sequence and the presence of three cis-active elements, Ets-1, Lyf-1 and E2F in the remaining downstream 59 bp of sequence. Electrophoretic gel-mobility shift assays showed that differences in the binding of trans-acting factors to these three elements accounts for the tumor-specific expression of this gene. Finally, analysis by fluorescent in situ hybridization revealed that promoter A and the main body of the mouse γGH gene are located between A3 and A5 on chromosome 4. This is an interesting finding in light of our earlier results which located promoter B and two associated alternates of exon 1 of this gene on chromosome 17. © 2002 Elsevier Science B.V. All rights reserved.
Keywords:	controlled study; gene sequence; promoter region; exon; gene deletion; mutation; dna-binding proteins; proto-oncogene proteins; sequence deletion; nonhuman; genetic analysis; animal cell; mouse; animals; cell cycle proteins; mice; in situ hybridization, fluorescence; gene expression; transcription initiation; protein binding; transcription, genetic; tumor cells, cultured; assay; transcription factors; dna; transcription regulation; molecular sequence data; recombinant fusion proteins; murinae; base sequence; genome; dna flanking region; mutagenesis, site-directed; binding sites; luciferases; electrophoretic mobility shift assay; mutagenesis; chromosome 17; gene location; 3t3 cells; chromosome mapping; tissue specificity; gene expression regulation, enzymologic; gel electrophoresis; chromosome 4; proto-oncogene proteins c-ets; gamma-glutamyl hydrolase; promoter regions (genetics); gamma glutamyl hydrolase; e2f transcription factors; proto-oncogene protein c-ets-1; priority journal; article; γ-glutamyl hydrolase gene transcription; folate polyglutamate hydrolysis
Journal Title:	Gene
Volume:	291
Issue:	1-2
ISSN:	0378-1119
Publisher:	Elsevier Science, Inc.
Date Published:	2002-05-29
Start Page:	169
End Page:	176
Language:	English
DOI:	10.1016/s0378-1119(02)00593-0
PUBMED:	12095690
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0037193665&partnerID=40&md5=198e5405a8bca194de003911b51ee13b
Notes:	Export Date: 14 November 2014 -- Source: Scopus

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