The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas

Abstract

The mouse Polycomb-group gene, embryonic ectoderm development (eed), appears to regulate cellular growth and dierentiation in a developmental and tissue speci®c 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 CD25+ stage of thymocyte dierentiation. 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 ®ndings support the notion that Polycomb-group genes exert pleiotrophic eects dictated by developmental stage and cellular context.

Juxtaposed Polycomb complexes co-regulate vertebral identity

“…In the absence of allele-specific effects, data for l7Rn5 3345SB and l7Rn5 1989SB were combined. These results also suggested haploinsufficiency of the l7Rn5 1989SB allele in the homeotic pathways, which contrasted with its dominant-negative function in carcinogen-induced T-cell lymphoma development (Richie et al, 2002). and Bmi1 antisense cRNA probes (E,F).…”

“…Additional developmental functions of EED included the regulation of random and imprinted X chromosome inactivation (Wang et al, 2001;Mak et al, 2002;Plath et al, 2003;Silva et al, 2003; and genomic imprinting (Mager et al, 2003). Furthermore, eed mutant animals exhibited hematopoietic defects in the bone marrow and thymus (Lessard et al, 1999;Richie et al, 2002).…”

Epigenetic regulation of normal and malignant hematopoiesis

“…Since EZH2 requires the presence of the other PRC2, 3 and 4 members for HMT activity, it is not surprising that dysregulation of other PRC components may also be linked to tumorigenesis. Indeed, downregulation of the polycomb component EED is associated with an increase incidence of carcinogen-induced lymphoma (Richie et al, 2002). Similarly, dysregulation of BMI1 also affects the activity of the PRCs, and overexpression and overactivity of BMI1 has been associated with a variety of solid tumors including lung, breast, colon, prostate and neuroblastoma as well as in malignant hematopoiesis (Breuer et al, 2004;Glinsky et al, 2005;Steele et al, 2006).…”

Insights Into Stem Cell Aging

“…Specifically, the Drosophila complex Psc (posterior sex combs), which includes Bmi1, and Suz12 (suppressor of zeste 12) play a tumor suppressive role mediated by Wnt repression in follicle stem cells (Li et al, 2010). In mammals, Eed (embryonic ectoderm development protein) displays tumor suppressive activity in the mouse hematopoietic system (Richie et al, 2002). Thus, PcG genes have been suggested to behave either as proto-oncogenes or as tumor suppressors depending on the tissue, cell context, developmental stage and gene dosage.…”