Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression

• Published in: Gene Vol. 377; pp. 1 - 5
• Main Authors: Faniello, Maria Concetta, Fregola, Annalisa, Nisticò, Antonia, Quaresima, Barbara, Crugliano, Telma, Faraonio, Raffaella, Puzzonia, Pasquale, Baudi, Francesco, Parlato, Giuseppe, Cuda, Giovanni, Morrone, Giovanni, Venuta, Salvatore, Costanzo, Francesco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2006
• Subjects: Alleles; Base Sequence; Binding Sites - genetics; CCAAT-Binding Factor - metabolism; DNA - genetics; DNA - metabolism; Ferritins - genetics; Gene Expression; HeLa Cells; Humans; In Vitro Techniques; NF-Y; Polymorphism, Single Nucleotide; Polymorphisms; Promoter Regions, Genetic; Protein Binding; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sp1 Transcription Factor - metabolism; Transcription, Genetic; Transcriptional regulation; NF-Y; w.t; Polymorphisms; Transcriptional regulation; βGal
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2006.02.034

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.