Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation

Hong Kai Ji, George Wu, Xiangcan Zhan, Alexandra Nolan, Cheryl Koh, Angelo Michael Demarzo, Hoang Mai Doan, Jinshui Fan, Christopher Cheadle, Mohammad Fallahi, John L. Cleveland, Chi V. Dang, Karen I. Zeller

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere26057
JournalPLoS One
Volume6
Issue number10
DOIs
StatePublished - 2011

Fingerprint

Biomass
biomass production
Genes
Stem cells
myc Genes
lymphoma
B-Cell Lymphoma
Transcription Factors
Bearings (structural)
genes
Cells
cells
Neoplasms
embryonic stem cells
Lymphocytes
Molecular Sequence Annotation
Microarrays
neoplasms
B-lymphocytes
Ewing's Sarcoma

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation. / Ji, Hong Kai; Wu, George; Zhan, Xiangcan; Nolan, Alexandra; Koh, Cheryl; Demarzo, Angelo Michael; Doan, Hoang Mai; Fan, Jinshui; Cheadle, Christopher; Fallahi, Mohammad; Cleveland, John L.; Dang, Chi V.; Zeller, Karen I.

In: PLoS One, Vol. 6, No. 10, e26057, 2011.

Research output: Contribution to journalArticle

Ji, HK, Wu, G, Zhan, X, Nolan, A, Koh, C, Demarzo, AM, Doan, HM, Fan, J, Cheadle, C, Fallahi, M, Cleveland, JL, Dang, CV & Zeller, KI 2011, 'Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation', PLoS One, vol. 6, no. 10, e26057. https://doi.org/10.1371/journal.pone.0026057
Ji, Hong Kai ; Wu, George ; Zhan, Xiangcan ; Nolan, Alexandra ; Koh, Cheryl ; Demarzo, Angelo Michael ; Doan, Hoang Mai ; Fan, Jinshui ; Cheadle, Christopher ; Fallahi, Mohammad ; Cleveland, John L. ; Dang, Chi V. ; Zeller, Karen I. / Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation. In: PLoS One. 2011 ; Vol. 6, No. 10.
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