R. Li et al., EXPRESSION OF THE HUMAN CYTOCHROME C1 GENE IS CONTROLLED THROUGH MULTIPLE SP1-BINDING SITES AND AN INITIATOR REGION, European journal of biochemistry, 241(2), 1996, pp. 649-656
It is widely accepted that nuclear genes that encode proteins of the o
xidative-phosphorylation system are regulated by nuclear factors belie
ved to be specific for such genes. In the present study we show that t
he promoter for the human cytochrome c1 gene is an exception, in that
it involves only conserved Sp1 core elements and an initiator region.
Maximal promoter activity within a 1.4-kb 5' flanking region of the cy
tochrome cl gene is contained in a fragment (-72 to +18) that lacks TA
TA and CCAAT elements. The transcriptional start site was mapped to an
initiator region by RNase protection of mRNA from human HepG2 cells,
and by primer extension of in vitro-generated transcripts, to a sequen
ce that is highly similar to the dihydrofolate reductase family of ini
tiators. Deletion of this region (+1 to +18) severely impairs transcri
ption initiation. Sp1 core elements centered at nucleotides -21 and -3
9 define the activation domain of the proximal promoter. Only the -39
element is protected from DNase I in the presence of crude nuclear ext
racts. However, transfection, gel-mobility-shift, supershift and in vi
tro-transcription experiments show that the -21 element binds Spl prot
ein and contributes to transcription activation. No other function al
oxidative-phosphorylation-specific response elements have been identif
ied. These data implicate Sp1 as a single activating factor for an oxi
dative-phosphorylation gene.