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A functional interaction between ATF7 and TAF12 that is modulated by TAF4
Pierre-Jacques Hamard1, Rozenn Dalbies-Tran, Charlotte Hauss
1Ecole Supérieure de Biotechnologie de Strasbourg, Université Louis Pasteur, Parc d'innovation, UMR7100 CNRS-ULP, Bd. Sebastien Brant-BP10413, 67412 Strasbourg, Illkirch Cedex, France.
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 hsTAF(II)20/15), 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 TAF(II)20 and TAF(II)15) interact with the ATF7 activation region through their histone-fold domain, only the largest, hsTAF12-1, mediates transcriptional activation through its N-terminal region.
Insights
Activating transcription factor 7 (ATF7) interacts with TAF12, a component of the general transcription factor TFIID. This interaction enhances ATF7
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcription Factors
Background:
- Activating transcription factor 7 (ATF7) is a versatile transcription factor.
- ATF7 interacts with adenovirus E1a, Jun, Fos, and JNK2.
- hsTAF12 is a component of the general transcription factor TFIID.
Purpose of the Study:
- To investigate the functional relationship between ATF7 and hsTAF12.
- To determine if TAF12 is a functional partner of ATF7.
Main Methods:
- Overexpression studies to assess transcriptional activation.
- Direct interaction assays.
- Chromatin immunoprecipitation (ChIP) to confirm in vivo interaction.
- Competitive inhibition assays using TAF4.
Main Results:
- Overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation via direct interaction.
- ATF7 and TAF12 interact on an ATF7-responsive promoter in vivo.
- TAF4 competitively inhibits TAF12-dependent transcriptional activation.
- Both TAF12 isoforms interact with ATF7's activation region via their histone-fold domain.
- Only the larger hsTAF12-1 isoform mediates transcriptional activation through its N-terminal region.
Conclusions:
- TAF12 is a functional partner of ATF7, enhancing its transcriptional activity.
- The interaction between ATF7 and TAF12 is crucial for gene regulation.
- Specific isoforms and domains of TAF12 play distinct roles in mediating ATF7 function.
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