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The Journal of Immunology, 2005, 174: 2507-2516.
Copyright © 2005 by The American Association of Immunologists

Polycomb Group Gene mel-18 Regulates Early T Progenitor Expansion by Maintaining the Expression of Hes-1, a Target of the Notch Pathway1

Masaki Miyazaki*, Hiroshi Kawamoto§, Yuko Kato*, Manami Itoi, Kazuko Miyazaki{ddagger}, Kyoko Masuda||, Satoshi Tashiro{dagger}, Hiroto Ishihara*, Kazuhiko Igarashi{dagger}, Takashi Amagai, Rieko Kanno* and Masamoto Kanno2,*

Departments of * Immunology and {dagger} Biomedical Chemistry, Graduate School of Biomedical Science, and {ddagger} Department of Developmental Biology, Research Institute for Radiation and Medicine, Hiroshima University, Hiroshima, Japan; § Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; Department of Immunology and Microbiology, Meiji University of Oriental Medicine, Kyoto, Japan; and || Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan

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.




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