Abstract
The ATF7 proteins, which are members of the cyclic AMP responsive binding protein (CREB)/activating transcription factor (ATF) family of transcription factors, display quite versatile properties: they can interact with the adenovirus E1a oncoprotein, mediating part of its transcriptional activity; they heterodimerize with the Jun, Fos or related transcription factors, likely modulating their DNA-binding specificity; they also recruit to the promoter a stress-induced protein kinase (JNK2). In the present study, we investigate the functional relationships of ATF7 with hsTAF12 (formerly hsTAFII20/15), which has originally been identified as a component of the general transcription factor TFIID. We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7. In support of this conclusion, chromatin immunoprecipitation experiments confirm the interaction of ATF7 with TAF12 on an ATF7-responsive promoter, in the absence of any artificial overexpression of both proteins. We also show that the TAF12-dependent transcriptional activation is competitively inhibited by TAF4. Although both TAF12 isoforms (TAF12-1 and -2, formerly TAFII20 and TAFII15) interact with the ATF7 activation region through their histone-fold domain, only the largest, hsTAF12-1, mediates transcriptional activation through its N-terminal region.
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Abbreviations
- ATF:
-
activating transcription factor
- TBP:
-
TATA-binding protein
- TAF:
-
TBP-associated factor
- HFD:
-
histone fold domain
- TFIID:
-
transcription factor IID
- IP:
-
immunoprecipitation
- MAP kinase:
-
mitogen-activated protein kinase
- JNK:
-
Jun N-terminal kinase
- CREB:
-
cyclic AMP responsive binding protein
- b-LZ:
-
basic region leucine zipper
- CRE:
-
cyclic AMP responsive binding
- SAGA:
-
SPT-ADA-GCN5-acetyltransferase
- STAGA:
-
SPT3-TAF9-GCN5-L acetyltransferase
- PCAF:
-
p300/CREB-binding protein-associated factor
- TFTC:
-
TBP-free TAF-containing complex
- CMV:
-
cytomegalovirus
- TK:
-
thymidine kinase
- GST:
-
glutathione S-transferase
- HA:
-
hemaglutinin
- WB:
-
Western blot
- ChIP:
-
chromatin-immunoprecipitation
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Acknowledgements
We thank L Tora, YG Gangloff, G Mengus, T Oegelschläger and M Vigneron for gifts and helpful discussions. This work was supported by funds and/or fellowships from the Centre National de la Recherche Scientifique, the Institut National de la Recherche Médicale, the Université Louis Pasteur de Strasbourg, the French Ministry of Research, the Association pour la Recherche sur le Cancer (contracts 5701 and 4521) and the Ligue Nationale contre le Cancer – Comités Alsace et Vosges.
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Hamard, PJ., Dalbies-Tran, R., Hauss, C. et al. A functional interaction between ATF7 and TAF12 that is modulated by TAF4. Oncogene 24, 3472–3483 (2005). https://doi.org/10.1038/sj.onc.1208565
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DOI: https://doi.org/10.1038/sj.onc.1208565