How c-Myc Regulates Nucleotide Metabolism
Author Information
Author(s): Liu Yen-Chun, Li Feng, Handler Jesse, Huang Cheng Ran Lisa, Xiang Yan, Neretti Nicola, Sedivy John M., Zeller Karen I., Dang Chi V.
Primary Institution: Johns Hopkins University School of Medicine
Hypothesis
Does c-Myc directly regulate nucleotide biosynthetic genes?
Conclusion
c-Myc directly induces nucleotide metabolic genes, which is essential for DNA replication and cell proliferation.
Supporting Evidence
- c-Myc directly binds to nucleotide biosynthetic gene promoters.
- Loss of IMPDH function leads to cell growth inhibition and apoptosis.
- MPA treatment causes S-phase arrest in cells with high c-Myc expression.
- Direct Myc target genes include IMPDH1 and IMPDH2, which are crucial for nucleotide metabolism.
- Gene expression analysis shows that nucleotide biosynthesis genes are upregulated by c-Myc.
Takeaway
c-Myc helps cells grow by controlling the production of building blocks needed for DNA. If these building blocks are not balanced, cells can get stressed and die.
Methodology
The study used chromatin immunoprecipitation (ChIP) and pair-end ditag sequencing to identify c-Myc target genes and assessed their expression in various cell lines and mouse models.
Potential Biases
Potential bias due to the use of cycloheximide affecting gene expression.
Limitations
The MYC-ER system may introduce noise that complicates the identification of direct Myc target genes.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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