Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis.
Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis.
复制标题
DOI：
10.1016/j.stemcr.2018.02.002
复制
发表时间：
2018-04-10
影响因子：
5.9
通讯作者：
Tachibana M
中科院分区：
文献类型：
--
作者：
Kuroki S;Nakai Y;Maeda R;Okashita N;Akiyoshi M;Yamaguchi Y;Kitano S;Miyachi H;Nakato R;Ichiyanagi K;Shirahige K;Kimura H;Shinkai Y;Tachibana M
组蛋白H3赖氨酸9（H3 K9）甲基化在哺乳动物染色体中分布不均匀。然而，控制不均匀分布的分子机制及其生物学意义仍有待阐明。在这里，我们发现JMJD 1A和JMJD 1B优先靶向染色体基因密集区的H3 K9去甲基化，从而在常染色质中建立H3 K9低甲基化状态。JMJD 1A/JMJD 1B缺陷胚胎在植入后不久死亡，伴随着上胚层细胞死亡。此外，JMJD 1A和JMJD 1B的联合缺失导致胚胎干细胞（ESC）中代谢基因的表达紊乱和细胞快速死亡。这些结果表明，JMJD 1A/JMJD 1B介导的H3 K9去甲基化对早期胚胎发生和ESC维持具有关键作用。最后，遗传拯救实验阐明了G9 A引起的H3 K9过度甲基化是JMJD 1A/JMJD 1B缺失的ESC细胞死亡和基因表达紊乱的原因。我们总结了JMJD 1A和JMJD 1B的组合，通过建立正确的H3 K9甲基化表观基因组来确保早期胚胎发生和ESC活力。JMJD 1A/JMJD 1B对ESC存活具有冗余但重要的作用JMJD 1A/JMJD 1B靶向基因密集常染色质上的H3 K9去甲基化JMJD 1A/JMJD 1B和G9 A在调节H3 K9 me 2水平中起协同作用Kuroki et al. H3 K9去甲基化酶JMJD 1A和JMJD 1B是小鼠ESC存活和早期胚胎发生所必需的。JMJD 1A和JMJD 1B通过在基因密集的常染色质处使H3 K9去甲基化来确保转录的准确性。
Histone H3 lysine 9 (H3K9) methylation is unevenly distributed in mammalian chromosomes. However, the molecular mechanism controlling the uneven distribution and its biological significance remain to be elucidated. Here, we show that JMJD1A and JMJD1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin. JMJD1A/JMJD1B-deficient embryos died soon after implantation accompanying epiblast cell death. Furthermore, combined loss of JMJD1A and JMJD1B caused perturbed expression of metabolic genes and rapid cell death in embryonic stem cells (ESCs). These results indicate that JMJD1A/JMJD1B-meditated H3K9 demethylation has critical roles for early embryogenesis and ESC maintenance. Finally, genetic rescue experiments clarified that H3K9 overmethylation by G9A was the cause of the cell death and perturbed gene expression of JMJD1A/JMJD1B-depleted ESCs. We summarized that JMJD1A and JMJD1B, in combination, ensure early embryogenesis and ESC viability by establishing the correct H3K9 methylated epigenome. JMJD1A/JMJD1B have redundant but essential roles for ESC survival JMJD1A/JMJD1B target H3K9 demethylation at gene-dense euchromatin JMJD1A/JMJD1B and G9A play collaborative roles in tuning H3K9me2 levels Kuroki et al. showed that H3K9 demethylases JMJD1A and JMJD1B are redundantly but essentially required for ESC survival and early embryogenesis in mice. JMJD1A and JMJD1B ensure transcription accuracy by demethylating H3K9 at gene-dense euchromatin.
登录
查看更多内容
影响因子：
16.6
作者：
Abe, Yohei;Rozqie, Royhan;Matsumura, Yoshihiro;Kawamura, Takeshi;Nakaki, Ryo;Tsurutani, Yuya;Tanimura-Inagaki, Kyoko;Shiono, Akira;Magoori, Kenta;Nakamura, Kanako;Ogi, Shotaro;Kajimura, Shingo;Kimura, Hiroshi;Tanaka, Toshiya;Fukami, Kiyoko;Osborne, Timothy F.;Kodama, Tatsuhiko;Aburatani, Hiroyuki;Inagaki, Takeshi;Sakai, Juro
通讯作者：
Sakai, Juro
影响因子：
10.5
作者：
Tachibana, M;Ueda, J;Shinkai, Y
通讯作者：
Shinkai, Y
影响因子：
64.8
作者：
Tateishi, Keisuke;Okada, Yuki;Kallin, Eric M.;Zhang, Yi
通讯作者：
Zhang, Yi
影响因子：
10.5
作者：
Tachibana, M;Sugimoto, K;Shinkai, Y
通讯作者：
Shinkai, Y
影响因子：
4.8
作者：
Shirato, Haruki;Ogawa, Satoko;Takeuchi, Takashi
通讯作者：
Takeuchi, Takashi