The transcriptional program of a human B cell line in response to Myc

Abstract

The proto-oncogene c-myc (myc) encodes a transcription factor (Myc) that promotes growth, proliferation and apoptosis. Myc has been suggested to induce these effects by induction/repression of downstream genes. Here we report the identification of potential Myc target genes in a human B cell line that grows and proliferates depending on conditional myc expression. Oligonucleotide microarrays were applied to identify downstream genes of Myc at the level of cytoplasmic mRNA. In addition, we identified potential Myc target genes in nuclear run-on experiments by changes in their transcription rate. The identified genes belong to gene classes whose products are involved in amino acid/protein synthesis, lipid metabolism, protein turnover/folding, nucleotide/DNA synthesis, transport, nucleolus function/RNA binding, transcription and splicing, oxidative stress and signal transduction. The identified targets support our current view that myc acts as a master gene for growth control and increases transcription of a large variety of genes.

N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation

“…Myc also represses genes that function to inhibit proliferation such as gas1 (Lee et al 1997), gadd45 (Marhin et al 1997), p15 Ink4b (Staller et al 2001), and p21 Cip1 (Gartel et al 2001). In addition to target genes involved in cell cycle progression, Myc has been found to stimulate expression of multiple genes that control cell size and growth, including those encoding ribosomal proteins, translation factors, and metabolic enzymes (Rosenwald et al 1993;Coller et al 2000;Guo et al 2000;Boon et al 2001;Schuhmacher et al 2001). The idea that Myc regulates cell growth is consistent with studies in Drosophila (Johnston et al 1999) as well as the effects of c-Myc overexpression in mammalian cells (Iritani and Eisenman 1999;Schuhmacher et al 1999;Beier et al 2000;Kim et al 2000).…”

Cyclin a but not cyclin D1 is essential for c‐myc‐modulated cell‐cycle progression

“…Our study demonstrated that the levels of cyclin A, D3, E, and kinase activities of complexes were increased in HEL cells in response to c-myc overexpression, and were decreased in A549 cells in response to c-myc expression inhibition. The effect of c-myc on cyclin D3 is positive (Schuhmacher et al, 2001), since cyclin D3-Cdk4 complexes trigger activation of cyclin E-Cdk2 by subtracting p21 and p27 from Cdk2 complexes (Sherr and Roberts, 1999) via a c-myc induced protein. These events appeared to be required for c-myc-driven cell proliferation (ZajacKaye, 2001).…”

“…Activation of cyclin-Cdk complexes is necessary and sufficient for the induction of cyclin A (Rudolph et al, 1996) by promoting the release of E2F (Schuhmacher et al, 2001). It seems that c-myc induces expression of cyclin D3, E, or Cdks, which in turn induces cyclin A expression.…”

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

“…This analysis revealed a significant correlation between low IC 50 (sensitivity to CDK9 inhibition) and four canonical transcriptional signatures of MYCdependent genes ( Fig. 4D; Supplemental Table 5; Coller et al 2000;Schuhmacher et al 2001;Zeller et al 2003;Schlosser et al 2005). MYC is a global regulator of gene expression that affects overall transcription, ribosomal biogenesis, protein translation, and cellular metabolism (Dang 2012;Conacci-Sorrell et al 2014), and, interestingly, transcripts overrepresented in sensitive compared with resistant cells were linked to ''gene expression,'' ''RNA metabolic process,'' and ''RNA processing'' ( Fig.…”