A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers

Mol Syst Biol. 2010 Jun 8;6:377. doi: 10.1038/msb.2010.31.

Abstract

Assembly of a transcriptional and post-translational molecular interaction network in B cells, the human B-cell interactome (HBCI), reveals a hierarchical, transcriptional control module, where MYB and FOXM1 act as synergistic master regulators of proliferation in the germinal center (GC). Eighty percent of genes jointly regulated by these transcription factors are activated in the GC, including those encoding proteins in a complex regulating DNA pre-replication, replication, and mitosis. These results indicate that the HBCI analysis can be used for the identification of determinants of major human cell phenotypes and provides a paradigm of general applicability to normal and pathologic tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Apoptosis / genetics
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism*
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • DNA Replication / genetics
  • Feedback, Physiological
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation
  • Gene Silencing
  • Genes, Regulator / genetics*
  • Germinal Center / cytology*
  • Germinal Center / metabolism*
  • Humans
  • Mitosis
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Transcription, Genetic

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Multiprotein Complexes
  • Proto-Oncogene Proteins c-myb