R. Wanner et al., THE PROMOTER OF THE HACAT KERATINOCYTE DIFFERENTIATION-RELATED GENE KERATIN-4 CONTAINS A FUNCTIONAL AP-2 BINDING-SITE, Archives of dermatological research, 289(12), 1997, pp. 705-708
The nuclear transcription factor AP-2 appears to be a key regulator me
diating programmed gene expression during embryonic morphogenesis and
adult cell differentiation. AP-2 has also been considered to be involv
ed in epidermal gene regulation, but its precise role is not yet defin
ed, The level of AP-2 transcripts increases during culturing of HaCaT
keratinocytes preceding the expression of the differentiation-related
gene keratin 4 (K4), The current study was aimed at investigating whet
her AP-2 transactivates K4 transcription, We cloned and sequenced the
promoter region of K4 and found, in addition to canonical sequences, a
n AP-2 consensus site in the vicinity of the transcriptional start, In
order to provide functional evidence for a regulation of K4 transcrip
tion by AP-2, we cloned various parts, which did or did not contain th
e AP-2 site of the K4 upstream sequence, into Cat reporter plasmids, T
hese constructs were ballistically transfected into differentiating Ha
CaT keratinocytes, The determination of the resulting Cat activity rev
ealed that the AP-2 site in the vicinity of the transcriptional start
was functional for K4 transcription, Thus, the role of AP-2 in the pro
cess of keratinocyte differentiation appears to be considerable, In ad
dition, further regulatory elements were found to be necessary for ful
l transcription of K4.