JDP2, a repressor of AP-1, recruits a histone deacetylase 3 complex to inhibit the retinoic acid-induced differentiation of F9 cells.
Up-regulation of the c-jun gene is a critical event in the retinoic acid (RA)-mediated differentiation of embryonal carcinoma F9 cells. Activating transcription factor 2 (ATF-2) and p300 cooperate in the activation of transcription of the c-jun gene during the differentiation of F9 cells. We show here that the overexpression of Jun dimerization protein 2 (JDP2), a repressor of AP-1, inhibits the transactivation of the c-jun gene by ATF-2 and p300 by recruitment of the histone deacetylase 3 (HDAC3) complex, thereby repressing the RA-induced transcription of the c-jun gene and inhibiting the RA-mediated differentiation of F9 cells. Moreover, chromatin immunoprecipitation assays showed that the JDP2/HDAC3 complex, which binds to the differentiation response element within the c-jun promoter in undifferentiated F9 cells, was replaced by the p300 complex in response to RA, with an accompanying change in the histone acetylation status of the chromatin, the initiation of transcription of the c-jun gene, and the subsequent differentiation of F9 cells. These results suggest that JDP2 may be a key factor that controls the commitment of F9 cells to differentiation and shed new light on the mechanism by which an AP-1 repressor functions.
Jin
Chunyuan
C
Gene Engineering Division, RIKEN Institute of Physical and Chemical Research, BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
Li
Hongjie
H
Murata
Takehide
T
Sun
Kailai
K
Horikoshi
Masami
M
Chiu
Robert
R
Yokoyama
Kazunari K
KK
D051698:Activating Transcription Factor 2; D000818:Animals; D018236:Carcinoma, Embryonal; D002454:Cell Differentiation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D016758:Genes, jun; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000099186:Histone Deacetylase 3
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D050881:E1A-Associated p300 Protein; D006655:Histone Deacetylases; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014212:Tretinoin; D000099186:Histone Deacetylase 3; C497106:Atf2 protein, mouse; C491386:Jundp2 protein, mouse; C494361:Ep300 protein, mouse