YY-1 and c-Jun transcription factors participate in the repression of the human involucrin promoter.
The human involucrin gene, which encodes a precursor of the keratinocyte cornified layer, is strongly expressed in response to differentiation stimuli. Earlier studies suggested that YY1 and components of the AP-1 family might participate in the silencing of involucrin in proliferating keratinocytes. This study shows that overexpression of either YY1 or c-Jun represses transcription of the human involucrin gene in multiplying keratinocytes. Transient overexpression and site-directed mutagenesis experiments of the involucrin 5'-non-coding region (5'-NCR) confirmed that YY1 and c-Jun repress involucrin transcription. This repression involves the distal zinc fingers of YY1 protein and the DNA binding and leucine zipper domains of c-Jun. The results with protein pull-down experiments are consistent with the hypothesis that interaction of YY1 with c-Jun is an important mechanism for involucrin repression. Cotransfection of YY1 modified the stimulatory function of mutant c-Jun proteins independently of their DNA binding capacity suggesting that interactions may be more complex in vivo. Additionally, c-Jun protein levels are affected by differentiation stimuli indicating the importance of c-Jun in the YY1 repression pathway. Thus YY1 and c-Jun have an important role in epidermal differentiation by negatively regulating the human involucrin gene.
Alvarez-Salas
L M
LM
Laboratorio de Terapia Génica, Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, México DF 07360, México. lalvarez@mail.cinvestav.mx
Benitez-Hess
M L
ML
Dipaolo
J A
JA
D020121:5' Untranslated Regions / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D004817:Epidermis / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D025941:Protein Interaction Mapping; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor; D016335:Zinc Fingers / Q000502:physiology
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011498:Protein Precursors; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C032253:involucrin