c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells

By Z. Nie, Gangqing Hu, Gang Wei, Kairong Cui, Arito Yamane, W. Resch, Ruoning Wang, Douglas R. Green, L. Tessarollo, R. Casellas and 2 more. Cell, 2012

1,104 citations recorded by the source corpus.

Summary 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 non-linear 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6780209f796862d107b989e5386d84ef996c5532

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Citations in the corpus

Transcriptional Amplification in Tumor Cells with Elevated c-Myc (2012, positive): “The results described here and by Nie et al. (2012) in this issue, support a different model: c-Myc accumulates in the promoter regions of active genes across the cancer cell genome and causes transcriptional amplification, producing increased levels of transcripts within the cell’s gene expression…”
MYC, metabolism, cell growth, and tumorigenesis. (2013, background): “High-quality MYC-binding sites are on the order of 10,000 or more per human genome, although MYC binding does not necessarily correlate with gene expression changes, particularly in systems in which MYC is inducible (Zeller et al. 2006; Kim et al. 2010; Lee et al. 2012; Lin et al. 2012; Nie et al. 2”
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming (2015, positive): “However, nucleosome-depleted targets were enriched for a less degenerate E-box motif that we and others have previously reported to be associated with c-Myc binding at enhancers (Lin et al., 2012; Nie et al., 2012; Soufi et al., 2012) (Figure 5B, single arrowhead in bottom panel).”
Transcriptional Regulation and its Misregulation in Disease (2013, positive): “In tumor cells expressing high levels of c-Myc, the transcription factor accumulates in the promoter regions of most active genes, recruits the transcription elongation factor P-TEFb, and causes transcriptional amplification, producing increased levels of transcripts within the cell’s gene expressio”
MYC, Metabolism, and Cancer. (2015, background): “As the low-throughput candidate gene or subtraction cloning approaches are replaced by unbiased genome-wide gene expression and chromatin immunoprecipitation (ChIP) analyses using next-generation sequencing, we now witness the entire spectrum of MYC’s transcriptional perturbation across the genome a”
Signal transduction in cancer. (2015, neutral): “Myc can thus serve as a universal amplifier of expressed genes rather than merely binding topromoters and initiating transcriptionde novo (Rahl et al. 2010; Lin et al. 2012; Nie et al. 2012).”
Transcriptional Addiction in Cancer (2017, positive): “MYC can have profound effects because it can function to amplify the entire gene expression program (Figure 4A) (Lin et al., 2012; Nie et al., 2012), and P53 is a powerful tumor suppressor because of its ability to arrest progress through the cell cycle or induce apoptosis (Lane and Levine, 2010).”
Selecting between‐sample RNA‐Seq normalization methods from the perspective of their assumptions (2016, background): “For example, a global shift has been observed in DE analysis with low and high c-Myc conditions [19, 20], and this shift was undetected without the use of spike-in controls [23].”
MYC activation is a hallmark of cancer initiation and maintenance. (2014, background): “The mechanistic basis for these differences may relate to the recent findings that MYC amplifies the output of previously activated gene expression programs (Lin et al. 2012; Nie et al. 2012; see Levens 2013 and Rahl and Young 2014).”