The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas.
The mouse Polycomb-group gene, embryonic ectoderm development (eed), appears to regulate cellular growth and differentiation in a developmental and tissue specific manner. During embryogenesis, eed regulates axial patterning, whereas in the adult eed represses proliferation of myeloid and B cell precursors. The present report demonstrates two novel functional activities of eed: alteration of thymocyte maturation and suppression of thymic lymphoma development. Mice that inherit the viable hypomorphic 17Rn5(1989SB) eed allele sustain a partial developmental block at or before the CD4(-)CD8(-)CD44(-)CD25(+) stage of thymocyte differentiation. Furthermore, mice that are homozygous or heterozygous for the hypomorphic eed allele have an increased incidence and decreased latency of N-methyl-N-nitrosourea-induced thymic lymphoma compared to wild-type littermates. These findings support the notion that Polycomb-group genes exert pleiotropic effects dictated by developmental stage and cellular context.
Richie
Ellen R
ER
Department of Carcinogenesis, The University of Texas, M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA. erichie@odin.mdacc.tmc.edu
Schumacher
Armin
A
Angel
Joe M
JM
Holloway
Marina
M
Rinchik
Eugene M
EM
Magnuson
Terry
T
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002454:Cell Differentiation / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D063151:Polycomb Repressive Complex 2; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*
D002273:Carcinogens; C107275:Eed protein, mouse; D012097:Repressor Proteins; D008770:Methylnitrosourea; D063151:Polycomb Repressive Complex 2