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Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
Published on: December 31, 2014
Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression
Daniel Y L Mao1, John D Watson, Pearlly S Yan
1Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Ontario M5G 2M9, Canada.
Abstract:
The c-myc proto-oncogene encodes a transcription factor, c-Myc, which is deregulated and/or overexpressed in many human cancers. Despite c-Myc's importance, the identity of Myc-regulated genes and the mechanism by which Myc regulates these genes remain unclear. By combining chromatin immunoprecipitation with CpG island arrays, we identified 177 human genomic loci that are bound by Myc in vivo. Analyzing a cohort of known and novel Myc target genes showed that Myc-associated protein X, Max, also bound to these regulatory regions. Indeed, Max is bound to these loci in the presence or absence of Myc. The Myc:Max interaction is essential for Myc-dependent transcriptional activation; however, we show that Max bound targets also include Myc-repressed genes. Moreover, we show that the interaction between Myc and Max is essential for gene repression to occur. Taken together, the identification and analysis of Myc bound target genes supports a model whereby Max plays an essential and universal role in the mechanism of Myc-dependent transcriptional regulation.
Insights
The transcription factor c-Myc regulates genes in cancer. Researchers found that Myc-associated protein X (Max) binds to these genes, playing a key role in both activating and repressing their transcription.
Area of Science:
- * Molecular Biology
- * Oncology
- * Gene Regulation
Background:
- * The c-myc proto-oncogene encodes the c-Myc transcription factor, frequently deregulated in human cancers.
- * Understanding Myc-regulated genes and their regulatory mechanisms is crucial for cancer research.
- * The precise role of Myc in transcriptional regulation requires further elucidation.
Purpose of the Study:
- * To identify genomic loci bound by Myc in vivo.
- * To investigate the role of Myc-associated protein X (Max) in Myc-mediated gene regulation.
- * To elucidate the mechanism of Myc-dependent transcriptional activation and repression.
Main Methods:
- * Chromatin immunoprecipitation combined with CpG island arrays to identify Myc binding sites.
- * Analysis of known and novel Myc target genes.
- * Investigation of Max binding to regulatory regions in the presence and absence of Myc.
Main Results:
- * Identified 177 human genomic loci bound by Myc in vivo.
- * Demonstrated that Max binds to these regulatory regions, irrespective of Myc presence.
- * Showed that the Myc:Max interaction is essential for both Myc-dependent gene activation and repression.
- * Identified Myc-repressed genes among Max-bound targets.
Conclusions:
- * Max plays an essential and universal role in Myc-dependent transcriptional regulation.
- * The Myc:Max complex is critical for both activating and repressing gene transcription.
- * This study provides a comprehensive model for Myc's function in gene regulation.
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