Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression.
Tissue-restricted POU domain transcription factors, which bind octamer or octamer-like gene sequences, play roles in cellular differentiation and the development of several organs. We have previously identified a POU domain gene, Skn-1a/i, expressed primarily in epidermis, that encodes at least two products through alternative splicing. One of these, Skn-1a, acts as a transcriptional activator, and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which prevents DNA-binding in vitro and transcriptional activation in vivo. We now demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an octamer site, suggesting that in vivo cellular factors modulate the activity of the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not allow transactivation by Skn-1i or by a heterologous transactivator containing this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are the major octamer-binding proteins in epidermis. Since Skn-1a is primarily expressed in suprabasal cells of the epidermis, we have tested its possible role in the regulation of epidermal papillomaviruses. In transient transfection assays, Skn-1a and Tst-1 can activate the long control region of the epidermis-specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo transcription data, in vitro DNA binding studies identify three octamer-like sites, which are capable of binding Skn-1a, in the HPV-1A long control region. Mutations of all three octamer-like sites prevent transactivation by Skn-1a in transient transfection assays. Taken together, these results provide evidence that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression and epidermal differentiation.
Andersen
B
B
Division of Endocrinology and Metabolism, School and Department of Medicine, University of California at San Diego, La Jolla, California 92037-0648, USA.
Hariri
A
A
Pittelkow
M R
MR
Rosenfeld
M G
MG
D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D050816:Octamer Transcription Factor-6; D027383:Papillomaviridae / Q000235:genetics*; D012097:Repressor Proteins; D012867:Skin / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; C494178:POU3F1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6