Telomere shortening by transgenerational transmission of TNF-α-induced TERRA via ATF7.
Telomere shortening by transgenerational transmission of TNF-α-induced TERRA via ATF7.
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DOI：
10.1093/nar/gky1149
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发表时间：
2019-01-10
影响因子：
14.9
通讯作者：
Ishii S
中科院分区：
文献类型：
--
作者：
Liu B;Maekawa T;Yoshida K;Ly NH;Inoue K;Hasegawa A;Chatton B;Ogura A;Ishii S
各种压力增加了疾病的易感性，加速了衰老，越来越多的证据表明，这些影响可以代代相传。流行病学研究表明，父母经历的压力源可能通过调节端粒动态来影响后代的寿命。端粒被端粒酶延长，并被某些应激以及端粒重复序列RNA（TERRA）缩短，端粒转录本。然而，对跨代影响的机制知之甚少。在这里，我们表明，TNF-α，这是由各种心理应激诱导，诱导p38依赖性磷酸化的ATF 7，应激反应的染色质调节，在小鼠睾丸生殖细胞。这导致ATF 7从端粒下区域的TERRA基因启动子中释放，从而破坏异染色质并诱导TERRA。TERRA通过精子传递给受精卵，引起端粒缩短。这些结果表明，ATF 7和TERRA在父系应激诱导的后代端粒缩短中起关键作用。
Various stresses increase disease susceptibility and accelerate aging, and increasing evidence suggests that these effects can be transmitted over generation. Epidemiological studies suggest that stressors experienced by parents affect the longevity of their offspring, possibly by regulating telomere dynamics. Telomeres are elongated by telomerase and shortened by certain stresses as well as telomere repeat-containing RNA (TERRA), a telomere transcript. However, the mechanism underlying the transgenerational effects is poorly understood. Here, we show that TNF-α, which is induced by various psychological stresses, induces the p38-dependent phosphorylation of ATF7, a stress-responsive chromatin regulator, in mouse testicular germ cells. This caused a release of ATF7 from the TERRA gene promoter in the subtelomeric region, which disrupted heterochromatin and induced TERRA. TERRA was transgenerationally transmitted to zygotes via sperm and caused telomere shortening. These results suggest that ATF7 and TERRA play key roles in paternal stress-induced telomere shortening in the offspring.
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影响因子：
25
作者：
Gapp, Katharina;Jawaid, Ali;Sarkies, Peter;Bohacek, Johannes;Pelczar, Pawel;Prados, Julien;Farinelli, Laurent;Miska, Eric;Mansuy, Isabelle M.
通讯作者：
Mansuy, Isabelle M.
影响因子：
3.6
作者：
Choi, YH;Toyoda, Y
通讯作者：
Toyoda, Y
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim
后代的白细胞端粒长度，父亲时代和精子中的端粒伸长率。
影响因子：
4.5
作者：
Kimura, Masayuki;Cherkas, Lynn F.;Kato, Bernet S.;Demissie, Serkalem;Hjelmborg, Jacob B.;Brimacombe, Michael;Cupples, Adrienne;Hunkin, Janice L.;Gardner, Jefferey P.;Lu, Xiaobin;Cao, Xiaojian;Sastrasinh, Malinee;Province, Michael A.;Hunt, Steven C.;Christensen, Kaare;Levy, Daniel;Spector, Tim D.;Aviv, Abraham
通讯作者：
Aviv, Abraham
影响因子：
56.9
作者：
Jia, ST;Noma, K;Grewal, SIS
通讯作者：
Grewal, SIS