title: Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.
abstract: The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.
authors: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. hji@jhsph.edu
authors: Hongkai
authors: H
authors: Ji
authors: George
authors: G
authors: Wu
authors: Xiangcan
authors: X
authors: Zhan
authors: Alexandra
authors: A
authors: Nolan
authors: Cheryl
authors: C
authors: Koh
authors: Angelo
authors: A
authors: De Marzo
authors: Hoang Mai
authors: HM
authors: Doan
authors: Jinshui
authors: J
authors: Fan
authors: Christopher
authors: C
authors: Cheadle
authors: Mohammad
authors: M
authors: Fallahi
authors: John L
authors: JL
authors: Cleveland
authors: Chi V
authors: CV
authors: Dang
authors: Karen I
authors: KI
authors: Zeller
mesh_terms: D000818:Animals; D018533:Biomass; D047369:Chromatin Immunoprecipitation; D016259:Genes, myc; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis