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

Masaki Miyazaki, Hiroshi Kawamoto, Yuko Kato, Manami Itoi, Kazuko Miyazaki, Kyoko Masuda, Satoshi Tashiro, Hiroto Ishihara, Kazuhiko Igarashi, Takashi Amagai, Rieko Kanno, Masamoto Kanno

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)2507-2516
Number of pages10
JournalJournal of Immunology
Volume174
Issue number5
DOIs
Publication statusPublished - 2005 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Miyazaki, M., Kawamoto, H., Kato, Y., Itoi, M., Miyazaki, K., Masuda, K., Tashiro, S., Ishihara, H., Igarashi, K., Amagai, T., Kanno, R., & Kanno, M. (2005). Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the notch pathway. Journal of Immunology, 174(5), 2507-2516. https://doi.org/10.4049/jimmunol.174.5.2507