Synergistic activation of human involucrin gene expression by Fra-1 and p300--evidence for the presence of a multiprotein complex.
Involucrin is expressed in the differentiated suprabasal epidermal layers, and an AP1 transcription factor-binding site present in the involucrin promoter distal regulatory region is required for this regulation. This site binds Fra-1, but cofactor interaction at this site has not been adequately characterized. We show that Fra-1 and p300 histone acetyltransferase are present at the AP1 site, as detected by chromatin immunoprecipitation. This interaction is functional, as treating p300 expressing keratinocytes with calcium or 12-O-tetradeconylphorbol-13-acetate, results in a synergistic increase in hINV expression, and this enhanced activation can be reproduced by coexpression of Fra-1 and p300. p300 also co-precipitates with Fra-1, but protein fractionation studies suggest that this interaction requires an additional protein. Fra-1 also interacts with other proteins that interact at the AP1-5 site, including JunD, JunB, Sp1, and P/CAF. Contrary to results in some other systems, Fra-1 functions as a positive transcriptional regulator in human keratinocytes. These studies suggest that a large multiprotein complex, which includes Fra-1, p300, P/CAF, junD, junB, and Sp1 acts at the AP1-5 site to produce a synergistic increase in hINV gene expression.
Crish
James F
JF
Department of Physiology and Biophysics, Case School of Medicine, Cleveland, Ohio, USA.
Eckert
Richard L
RL
D002118:Calcium / Q000494:pharmacology; D000078404:Epidermal Cells; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D046912:Multiprotein Complexes / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099169:Fos-Related Antigen 1; D000099224:p300-CBP-Associated Factor
D002118:Calcium; D046912:Multiprotein Complexes; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D050880:p300-CBP Transcription Factors; D000099169:Fos-Related Antigen 1; D000099224:p300-CBP-Associated Factor; C032253:involucrin