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Published on: June 6, 2025
c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells
Zuqin Nie1, Gangqing Hu, Gang Wei
1Laboratory of Pathology, NCI, Bethesda, MD 20892, USA.
Abstract:
The c-Myc HLH-bZIP protein has been implicated in physiological or pathological growth, proliferation, apoptosis, metabolism, and differentiation at the cellular, tissue, or organismal levels via regulation of numerous target genes. No principle yet unifies Myc action due partly to an incomplete inventory and functional accounting of Myc's targets. To observe Myc target expression and function in a system where Myc is temporally and physiologically regulated, the transcriptomes and the genome-wide distributions of Myc, RNA polymerase II, and chromatin modifications were compared during lymphocyte activation and in ES cells as well. A remarkably simple rule emerged from this quantitative analysis: Myc is not an on-off specifier of gene activity, but is a nonlinear amplifier of expression, acting universally at active genes, except for immediate early genes that are strongly induced before Myc. This rule of Myc action explains the vast majority of Myc biology observed in literature.
Insights
The c-Myc protein amplifies gene expression, not simply turning genes on or off. This finding offers a unifying principle for understanding c-Myc
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The c-Myc (Myc) protein, a transcription factor, plays a crucial role in cell growth, proliferation, and apoptosis.
- Understanding Myc's regulatory mechanisms is vital due to its involvement in both normal physiological processes and pathological conditions like cancer.
- Current knowledge lacks a unifying principle to explain the diverse functions of Myc, partly due to an incomplete understanding of its target genes.
Purpose of the Study:
- To elucidate the regulatory role of the c-Myc protein in gene expression.
- To identify a unifying principle governing Myc's function in gene regulation.
- To investigate Myc's action in a system with temporal and physiological regulation.
Main Methods:
- Comparative analysis of transcriptomes and genome-wide distributions of Myc, RNA polymerase II, and chromatin modifications.
- Study conducted during lymphocyte activation and in embryonic stem (ES) cells.
- Quantitative analysis of gene expression patterns.
Main Results:
- Myc acts as a nonlinear amplifier of gene expression, rather than an on/off switch.
- Myc universally targets actively transcribed genes.
- Immediate early genes, strongly induced before Myc, are an exception to this rule.
Conclusions:
- A simple, unifying rule for Myc action has been identified: nonlinear amplification of gene expression at active genes.
- This rule explains a significant portion of observed Myc biology.
- Further research can build upon this principle to understand Myc's multifaceted roles in cellular processes.
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