Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression.
The H ferritin promoter spans approximately 150 bp, upstream of the transcription start and is composed by two cis-elements in position -132 (A box) and -62 (B-box), respectively. The A box is recognized by the transcription factor Sp1, and the B-box by a protein complex called Bbf, which includes the CAAT binding factor NF-Y. In this study we performed a functional analysis of an H ferritin promoter allele carrying a G to T substitution adjacent to the Bbf binding site, in position -69. In vitro studies with reporter constructs revealed a significantly reduced transcriptional activity of this allele compared to that of the w.t. promoter that was mirrored by a decrease in Bbf binding. In vivo, this variant genotype is accompanied by a reduced amount of the H mRNA in peripheral blood lymphocytes.
Faniello
Maria Concetta
MC
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università di Catanzaro Magna Graecia, Campus Universitario, Germaneto, Italy.
Fregola
Annalisa
A
Nisticò
Antonia
A
Quaresima
Barbara
B
Crugliano
Telma
T
Faraonio
Raffaella
R
Puzzonia
Pasquale
P
Baudi
Francesco
F
Parlato
Giuseppe
G
Cuda
Giovanni
G
Morrone
Giovanni
G
Venuta
Salvatore
S
Costanzo
Francesco
F
D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D023081:CCAAT-Binding Factor / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000235:genetics*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic
D023081:CCAAT-Binding Factor; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D004247:DNA; D005293:Ferritins