Complex interactions between epidermal POU domain and activator protein 1 transcription factors regulate the expression of the profilaggrin gene in normal human epidermal keratinocytes.
The human profilaggrin gene is expressed in the granular layer during the late stages of the epidermal differentiation. The proximal promoter region of the gene confers high levels of keratinocyte-specific transcription via interactions with c-Jun/c-Fos heterodimers. Here we provide evidence for another level of complexity in the regulation of the profilaggrin promoter activity. The POU domain proteins Oct1, Skn1a/i, and Oct6, which are abundantly expressed in the epidermal cells, act to both stimulate and repress transcription in a general and a cell type-specific mode. While binding to specific recognition elements within the promoter region, they exert their effects by either stimulating or antagonizing the c-Jun-dependent activity of the promoter. The response of the promoter to forced expression of the POU domain proteins reflects the effect of these transcription factors on the endogenous profilaggrin mRNA synthesis and suggests that the latter requires a fine balance in the amounts and the activities of the individual activator protein 1 and POU domain proteins.
Jang
S I
SI
Laboratory of Skin Biology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA.
Karaman-Jurukovska
N
N
Morasso
M I
MI
Steinert
P M
PM
Markova
N G
NG
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D006801:Humans; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D050816:Octamer Transcription Factor-6; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D000091344:Filaggrin Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D007381:Intermediate Filament Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; C494178:POU3F1 protein, human; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6