title: c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells.
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.
authors.affiliation: Laboratory of Pathology, NCI, Bethesda, MD 20892, USA.
authors.forename: Zuqin
authors.initials: Z
authors.lastname: Nie
authors.forename: Gangqing
authors.initials: G
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Ruoning
authors.initials: R
authors.lastname: Wang
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Levens
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D016678:Genome; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D015533:Transcriptional Activation
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012321:DNA-Directed RNA Polymerases