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Published on: October 6, 2016
Drosophila Myc interacts with host cell factor (dHCF) to activate transcription and control growth
Michael Furrer1, Mirjam Balbi, Monica Albarca-Aguilera
1Zoologisches Institut, Universität Zürich, 8057 Zürich, Switzerland.
Abstract:
The Myc proto-oncoproteins are transcription factors that recognize numerous target genes through hexameric DNA sequences called E-boxes. The mechanism by which they then activate the expression of these targets is still under debate. Here, we use an RNAi screen in Drosophila S2 cells to identify Drosophila host cell factor (dHCF) as a novel co-factor for Myc that is functionally required for the activation of a Myc-dependent reporter construct. dHCF is also essential for the full activation of endogenous Myc target genes in S2 cells, and for the ability of Myc to promote growth in vivo. Myc and dHCF physically interact, and they colocalize on common target genes. Furthermore, down-regulation of dHCF-associated histone acetyltransferase and histone methyltransferase complexes in vivo interferes with the Myc biological activities. We therefore propose that dHCF recruits such chromatin-modifying complexes and thereby contributes to the expression of Myc targets and hence to the execution of Myc biological activities.
Insights
Drosophila host cell factor (dHCF) acts as a novel co-factor for Myc. dHCF is essential for Myc
Area of Science:
- Molecular Biology
- Gene Regulation
- Cancer Research
Background:
- Myc proto-oncoproteins are transcription factors regulating gene expression via E-boxes.
- The precise mechanism of Myc-mediated transcriptional activation remains under investigation.
Purpose of the Study:
- To identify novel co-factors involved in Myc-mediated transcriptional activation.
- To elucidate the functional role of Drosophila host cell factor (dHCF) in Myc activity.
Main Methods:
- Conducted an RNAi screen in Drosophila S2 cells to identify Myc co-factors.
- Assessed the impact of dHCF depletion on Myc-dependent reporter gene expression.
- Investigated Myc-dHCF physical interaction and colocalization on target genes.
- Examined the effect of chromatin-modifying complexes on Myc and dHCF activities.
Main Results:
- Identified Drosophila host cell factor (dHCF) as a novel Myc co-factor.
- dHCF is functionally required for Myc-dependent reporter activation and endogenous gene expression in S2 cells.
- dHCF is essential for Myc-mediated growth promotion in vivo.
- Myc and dHCF physically interact and colocalize on target genes.
- Disruption of dHCF-associated histone acetyltransferase and methyltransferase complexes impairs Myc activity.
Conclusions:
- Propose that dHCF recruits chromatin-modifying complexes to Myc target genes.
- dHCF plays a crucial role in Myc-mediated transcriptional activation and biological functions.
- This finding provides new insights into the regulatory mechanisms of Myc.
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