Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells.
Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells.
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取得平衡：Zfp281 和 Mll2 在小鼠胚胎干细胞中调节转座元件
DOI：
10.1093/nar/gkx841
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发表时间：
2017-12-01
影响因子：
14.9
通讯作者：
Lin C
中科院分区：
文献类型：
--
作者：
Dai Q;Shen Y;Wang Y;Wang X;Francisco JC;Luo Z;Lin C
摘要转座因子（TE）约占小鼠基因组的40%。LINE-1（L1）等活性TE的逆转录转座极大地影响了遗传多样性和基因组稳定性。因此，逆转录转座子的转录和转座活性受到严格控制。在这里，我们表明，Krüppel样锌指蛋白Zfp 281直接结合和抑制逆转录转座子的子集，包括活跃的年轻L1重复元件，在小鼠胚胎干细胞（ES）。此外，我们发现Zfp 281调节的L1高度富集5-羟甲基胞嘧啶（5 hmC）和H3 K4 me 3。COMPASS样H3 K4甲基转移酶Mll 2是Zfp 281调节的L1处的主要H3 K4 me 3甲基化酶，并且是其适当表达所需的。我们的研究还表明，Zfp 281的功能部分是通过招募L1调节DNA羟甲基化酶Tet 1和Sin 3A，并限制Mll 2在这些活跃的L1，导致他们的平衡表达。总之，我们的数据表明Zfp 281在抑制小鼠ES细胞中的年轻活性L1中的工具作用。
Abstract Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells.
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影响因子：
16.8
作者：
Hu D;Garruss AS;Gao X;Morgan MA;Cook M;Smith ER;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
通讯作者：
Walichiewicz, J
影响因子：
64.8
作者：
Jacobs, Frank M. J.;Greenberg, David;Ngan Nguyen;Haeussler, Maximilian;Ewing, Adam D.;Katzman, Sol;Paten, Benedict;Salama, Sofie R.;Haussler, David
通讯作者：
Haussler, David
影响因子：
23.9
作者：
Fidalgo, Miguel;Huang, Xin;Guallar, Diana;Sanchez-Priego, Carlos;Valdes, Victor Julian;Saunders, Arven;Ding, Junjun;Wu, Wen-Shu;Clavel, Carlos;Wang, Jianlong
通讯作者：
Wang, Jianlong
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O