c-Jun and Sp1 family are critical for retinoic acid induction of the lamin A/C retinoic acid-responsive element.
The expression of A-type lamins, subdivided into lamin A and C, is developmentally regulated. Retinoic acid (RA)-induced differentiation of P19 embryonic carcinoma cells, in which A-type lamins are absent, increases the expression of lamin A/C. We previously showed, using P19 cells as a model system, that the lamin A/C promoter has a retinoic acid-responsive element (L-RARE), and that Sp1 and Sp3 bind the CACCC box of the L-RARE. In this study, we report that Sp1, Sp3, and c-Jun increase transactivation of the L-RARE during RA treatment. Sp1 and Sp3 regulate the lamin A/C promoter in Sp1-deficient SL2 cells and contribute to RA-dependent activation in GAL4-based transcriptional assays. Overexpression of c-Jun causes transactivation of a chimeric promoter consisting of four tandem L-RARE repeats fused with the luciferase gene in P19 cells. c-Jun also transactivates a reporter construct with five tandem GAL4-binding sites, only when co-expressed with either GAL4-Sp1 or Sp3 fusion proteins. Furthermore, we detect a physiological interaction between c-Jun with Sp1/Sp3 in RA-treated cells. Our data suggest that Sp1, Sp3, and c-Jun play an important role in gene expression through the L-RARE during RA treatment.
Okumura
Koichi
K
Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan. kokumura@ucsd.edu
Hosoe
Yuko
Y
Nakajima
Noboru
N
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D034904:Lamin Type A / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
D034904:Lamin Type A; D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; C440308:lamin C; D014212:Tretinoin