Characterization and functional analysis of cis-acting elements of the human farnesyl diphosphate synthetase (FDPS) gene 5' flanking region.
Farnesyl diphosphate synthetase (FDPS) is a key enzyme in the isoprenoid pathway responsible for cholesterol biosynthesis, post-translational protein modifications and synthesis of steroid hormones, whose expression is regulated by phorbol esters and polyunsaturated fatty acids. Genomic comparison of the 5' upstream sequence of the FDPS genes identifies conserved binding sites for NF-Y, SP1, SRE3, and YY1 regulatory elements in rat, mouse, dog and chimpanzee. Two additional specific consensus sequences, upstream of the core promoter that had not been analysed previously, are shared only by human and chimpanzee genomes. The work presented here aimed at characterizing these genomic sequence elements in the human FDPS promoter region and their contribution to gene expression. We have characterized functionally the minimal basal promoter of the human FDPS gene by means of deletion mutants and we have identified two cis-acting elements which modulate the FDPS gene expression and are recognized by Pax5 and OCT-1 transcription factors.
Romanelli
Maria Grazia
MG
Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy. mariagrazia.romanelli@univr.it
Lorenzi
Pamela
P
Sangalli
Antonella
A
Diani
Erica
E
Mottes
Monica
M
D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D015971:Gene Expression Regulation, Enzymologic; D051228:Geranyltranstransferase / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment
D020121:5' Untranslated Regions; D050811:Octamer Transcription Factor-1; D051757:PAX5 Transcription Factor; D051228:Geranyltranstransferase