Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway.
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.
Miyazaki
Masaki
M
Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Kawamoto
Hiroshi
H
Kato
Yuko
Y
Itoi
Manami
M
Miyazaki
Kazuko
K
Masuda
Kyoko
K
Tashiro
Satoshi
S
Ishihara
Hiroto
H
Igarashi
Kazuhiko
K
Amagai
Takashi
T
Kanno
Rieko
R
Kanno
Masamoto
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005333:Fetus; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C066476:Pcgf6 protein, mouse