TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells.

TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells.
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DOI:
10.1016/j.celrep.2014.12.004
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发表时间:
2015-01-06
期刊:
影响因子:
8.8
通讯作者:
Jakobsson J
Jakobsson J
中科院分区:
生物学1区
文献类型:
--
作者:
Fasching L;Kapopoulou A;Sachdeva R;Petri R;Jönsson ME;Männe C;Turelli P;Jern P;Cammas F;Trono D;Jakobsson J

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TRIM28是一种辅阻遏子,通过建立局部异染色质来介导转录沉默。在这里,我们发现在神经前体细胞中TRIM28的缺失导致两组内源性逆转录病毒(ERV)的高水平表达:IAP1和MMERVK10C。我们发现,NPC使用TRIM28介导组蛋白修饰来动态调节ERV的转录和沉默,这与其他使用DNA甲基化的体细胞类型形成了鲜明对比。我们还表明,ERV的去抑制通过激活附近的基因和表达长的非编码RNA来影响NPC的转录动力学。这些发现证明了鼻咽癌中ERV的独特动态转录调控。我们的结果保证了未来对ERV在健康和患病大脑中的作用的研究。
TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.
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