Regulating retrotransposon activity through the use of alternative transcription start sites
Regulating retrotransposon activity through the use of alternative transcription start sites
复制标题
通过使用替代转录起始位点调节逆转录转座子活性
作者：
Jenna Persson;Babett Steglich;Agata Smialowska;Mette Boyd;Jette Bornholdt;R. Andersson;C. Schurra;B. Arcangioli;A. Sandelin;O. Nielsen;K. Ekwall
逆转录转座子是逆转录病毒的祖先，如果不加以控制，就有可能破坏基因和接管基因组。有趣的是，尽管宿主细胞通过多种机制抑制这些元件，但它们在应激条件下被转录甚至被激活。在这里，我们描述了一个新的机制，逆转录转座子调节通过转录起始位点（TSS）的选择改变核小体占用。我们发现，Fun30染色质重塑合作，以保持高水平的核小体占用在反转录转座子侧翼长末端重复序列（LTR）元件。这强制使用下游TSS并产生不能逆转录和反转录转座的截短RNA。然而，在应激细胞中，LTR元件处的核小体占据减少，并且TSS移位以允许生产性转录。我们提出，来自非生产性TSS的受控反转录转座子转录允许快速应激诱导的激活，同时防止基因组中不受控制的转座子活性。
Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon‐flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress‐induced activation, while preventing uncontrolled transposon activity in the genome.
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影响因子：
7
作者：
Malik, HS;Henikoff, S;Eickbush, TH
通讯作者：
Eickbush, TH
影响因子：
11.8
作者：
Peaston, AE;Evsikov, AV;Knowles, BB
通讯作者：
Knowles, BB
影响因子：
3.7
作者：
Easley R;Carpio L;Dannenberg L;Choi S;Alani D;Van Duyne R;Guendel I;Klase Z;Agbottah E;Kehn-Hall K;Kashanchi F
通讯作者：
Kashanchi F
影响因子：
16
作者：
Rowbotham, Samuel P.;Barki, Leila;Mermoud, Jacqueline E.
通讯作者：
Mermoud, Jacqueline E.