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Updated: Sep 26, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for
Xiaohui Liu1, Jerusalem Tesfai, Yvonne A Evrard
1Department of Biochemistry, University of California, Riverside 92521, USA.
Abstract:
Deregulation of the c-Myc oncoprotein (Myc) is implicated in many types of cancer. Myc is a sequence-specific transcription factor that regulates transcription of genes involved in the control of cell proliferation and apoptosis via mechanisms that are still poorly understood. Cell transformation by Myc involves its association with the transformation-transactivation domain-associated protein (TRRAP) and the human histone acetyltransferase (HAT) GCN5. TRRAP and GCN5 are components of a variety of shared and distinct multiprotein HAT complexes with diverse functions. Myc induces TRRAP recruitment and histone hyperacetylation at specific Myc-activated genes in vivo. However, the identity of the HAT complexes recruited by Myc and the roles of TRRAP and GCN5 in Myc function are still unclear. Here we show that Myc co-recruits TRRAP and GCN5 via direct physical interactions of its N-terminal activation/transformation domain with the human STAGA (SPT3-TAF-GCN5 acetylase) coactivator complex. We demonstrate that GCN5 and TRRAP cooperate to enhance transcription activation by the N-terminal activation domain of Myc in vivo and that this synergy requires both the SPT3/GCN5 interaction domain of TRRAP and the HAT activity of GCN5. Thus, TRRAP might function as an adaptor within the STAGA complex, which helps recruit GCN5 HAT activity to Myc during transcription activation.
Insights
The c-Myc oncoprotein (Myc) recruits the STAGA complex, including TRRAP and GCN5, to activate gene transcription in cancer. This interaction enhances cell proliferation and apoptosis control.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Deregulation of c-Myc oncoprotein (Myc) is a key factor in numerous cancers.
- Myc functions as a transcription factor controlling cell proliferation and apoptosis, but its mechanisms are not fully understood.
- Myc's role in cell transformation involves interactions with TRRAP and GCN5, components of histone acetyltransferase (HAT) complexes.
Purpose of the Study:
- To identify the specific HAT complexes recruited by Myc.
- To elucidate the roles of TRRAP and GCN5 in Myc-mediated transcription activation.
- To investigate the physical interactions between Myc, TRRAP, GCN5, and the STAGA complex.
Main Methods:
- Investigated direct physical interactions between Myc's N-terminal domain and the STAGA coactivator complex.
- Assessed the cooperative effects of GCN5 and TRRAP on Myc-induced transcription activation in vivo.
- Determined the requirement of TRRAP's SPT3/GCN5 interaction domain and GCN5's HAT activity for synergistic transcription enhancement.
Main Results:
- Myc directly co-recruits TRRAP and GCN5 through interactions with the human STAGA complex.
- GCN5 and TRRAP synergistically enhance transcription activation mediated by Myc's N-terminal domain.
- This synergistic effect is dependent on the SPT3/GCN5 interaction domain of TRRAP and the HAT activity of GCN5.
Conclusions:
- Myc utilizes the STAGA complex, specifically TRRAP and GCN5, for transcriptional regulation.
- TRRAP acts as an adaptor within STAGA, facilitating GCN5 HAT recruitment to Myc during transcription activation.
- Understanding this mechanism provides insights into Myc's role in cancer and potential therapeutic targets.
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