Regulation of desmocollin gene expression in the epidermis: CCAAT/enhancer-binding proteins modulate early and late events in keratinocyte differentiation.
Desmocollins (Dscs) are desmosomal cadherins that exhibit differentiation-specific patterns of expression in the epidermis. Dsc3 expression is strongest in basal cell layers, whereas Dsc1 is largely confined to upper, terminally differentiating strata. To understand better the processes by which Dsc expression is regulated in the epidermis, we have isolated Dsc3 and Dsc1 5'-flanking DNAs and analysed their activity in primary keratinocytes. In the present study, we found that transcription factors of the CCAAT/enhancer-binding protein family play a role in the regulation of expression of both Dscs and, in so doing, implicate this class of transcription factors in both early and late events in keratinocyte differentiation. We show that Dscs are differentially regulated by C/EBP (CCAAT/enhancer-binding protein) family members, with Dsc3 expression being activated by C/EBPbeta but not C/EBPalpha, and the reverse being the case for Dsc1. Expression of both Dscs is activated by another family member, C/EBPdelta. These results show for the first time how desmosomal cadherin gene expression is regulated and provide a mechanism for the control of other differentiation-specific genes in the epidermis.
Smith
Conrad
C
Division of Medical Sciences, University of Birmingham, Clinical Research Block, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
Zhu
Kuichun
K
Merritt
Anita
A
Picton
Rhian
R
Youngs
Denise
D
Garrod
David
D
Chidgey
Martyn
M
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D051187:Desmocollins; D051180:Desmoplakins; D004817:Epidermis / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D003598:Cytoskeletal Proteins; D051187:Desmocollins; D051180:Desmoplakins