Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway

J Immunol. 2005 Mar 1;174(5):2507-16. doi: 10.4049/jimmunol.174.5.2507.


Polycomb group (PcG) proteins play a role in the maintenance of cellular identity throughout many rounds of cell division through the regulation of gene expression. In this report we demonstrate that the loss of the PcG gene mel-18 impairs the expansion of the most immature T progenitor cells at a stage before the rearrangement of the TCR beta-chain gene in vivo and in vitro. This impairment of these T progenitors appears to be associated with increased susceptibility to cell death. We also show that the expression of Hes-1, one of the target genes of the Notch signaling pathway, is drastically down-regulated in early T progenitors isolated from mel-18(-/-) mice. In addition, mel-18(-/-) T precursors could not maintain the Hes-1 expression induced by Delta-like-1 in monolayer culture. Collectively, these data indicate that mel-18 contributes to the maintenance of the active state of the Hes-1 gene as a cellular memory system, thereby supporting the expansion of early T progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Death / genetics
  • Cell Death / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Fetus
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Lymphocyte Count
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Male
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • Receptors, Notch
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Signal Transduction* / immunology
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Transcription Factor HES-1


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Membrane Proteins
  • Pcgf6 protein, mouse
  • Polycomb-Group Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Transcription Factor HES-1
  • Polycomb Repressive Complex 1