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Access through your institution Buy or subscribe Sabò, Kress, Pelizzola _et al_. investigated the role of MYC in gene expression during B cell lymphomagenesis using premalignant B cells from
young Eμ-_Myc_ mice and B lymphoma cells from adult Eμ-_Myc_ mice. By profiling MYC binding with chromatin immunoprecipitation followed by sequencing (ChIP–seq) the authors found that the
number of sites and the intensity of binding to genomic loci by MYC increased from premalignant B cells to B lymphoma cells, which correlated with increased levels of MYC. Moreover, MYC
bound to progressively larger proportions of active promoters and enhancers, with 87–94% of active promoters being bound by MYC in B lymphoma cells, an effect termed 'chromatin
invasion'. To assess whether MYC binding to these active promoters correlated with changes in gene expression, the authors used RNA-seq to identify all differentially expressed genes in
premalignant B cells and B lymphoma cells, compared with controls. The authors also digitally 'normalized' the gene expression data to mRNAs per cell. With these combined data, it
became clear that global RNA production increased in premalignant and B lymphoma cells, as would be predicted by the amplification model, but this co-existed with the relative upregulation
and downregulation of distinct subsets of mRNAs. To resolve whether selective gene regulation or transcriptional amplification are direct or indirect effects of MYC, the authors turned to
fibroblasts. Mitogenic stimulation of these cells yielded the same effects as in the B cells (global RNA amplification and selective gene regulation), but this occurred in the absence of
chromatin invasion, indicating that RNA amplification is an indirect effect of MYC. Most importantly, hyperactivation of MYC in dividing fibroblasts led it to invade chromatin without
inducing further RNA amplification, but rather the upregulation and downregulation of specific groups of genes. Altogether, the authors concluded that MYC is not a general transcriptional
amplifier but instead directly regulates the expression of distinct subsets of genes that lead to the indirect amplification of global transcripts through downstream effects of MYC-induced
genes. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online
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are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Sabò, A. et al. Selective
transcriptional regulation by Myc in cellular growth control and lymphomagenesis. _Nature_ http://dx.doi.org/10.1038/nature13537 (2014) * Walz, S. et al. Activation and repression by
oncogenic MYC shape tumour-specific gene expression profiles. _Nature_ http://dx.doi.org/10.1038/nature13473 (2014) Download references Authors * Gemma K. Alderton View author publications
You can also search for this author inPubMed Google Scholar RELATED LINKS RELATED LINKS RELATED LINKS IN NATURE RESEARCH Cunningham, J. T. _et al_. Protein and nucleotide biosynthesis are
coupled by a single rate-limiting enzyme, PRPS2, to drive cancer. _Cell_ 157, 1088–1103 (2014) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Alderton,
G. The transcriptional effects of MYC. _Nat Rev Cancer_ 14, 513 (2014). https://doi.org/10.1038/nrc3790 Download citation * Published: 24 July 2014 * Issue Date: August 2014 * DOI:
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