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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Proc+Natl+Acad+Sci+U+S+A 2016 ; 113 (37): 10370-5 Nephropedia Template TP
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Propagation of trimethylated H3K27 regulated by polycomb protein EED is required for embryogenesis, hematopoietic maintenance, and tumor suppression #MMPMID27578866
Ueda T; Nakata Y; Nagamachi A; Yamasaki N; Kanai A; Sera Y; Sasaki M; Matsui H; Honda Zi; Oda H; Wolff L; Inaba T; Honda H
Proc Natl Acad Sci U S A 2016[Sep]; 113 (37): 10370-5 PMID27578866show ga
Polycomb repressive complex 2 (PRC2) is a central regulator in all forms of histone H3 Lys27 (H3K27) methylation. Interaction of embryonic ectoderm development (EED) with trimethylated H3K27 (H3K27me3) is required for the allosteric activation of PRC2. We previously identified a myeloid disorder-associated EED Ile363Met (I363M) mutation with impaired binding ability to H3K27me3. By generating I363M knock-in mice, we demonstrated that I363M preferentially dampened the propagation of H3K27me3 repressive marks in vivo. The homozygotes caused embryonic lethality, whereas the heterozygotes enhanced hematopoietic stem/progenitor cell (HSPC) activity, coupled with susceptibility to leukemia. Lgals3, a PRC2 target gene, was derepressed by I363M, which enhanced the stemness of HSPCs. Our findings highlight the significance of the structural integrity of EED in cellular homeostasis and tumor suppression.