RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells

Ten-eleven translocation (TET) proteins play key roles in the regulation of DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Unlike the other members of the...

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Detalles Bibliográficos
Autores: Guallar Artal, Diana, Bi, Xianju, Pardavila Paz, Jose Ángel, Huang, Xin, Saenz, Carmen, Shi, Xianle, Zhou, Hongwei, Faiola, Francesco, Ding, Junjun, Haruehanroengra, Phensinee, Yang, Fan, Li, Dan, Sánchez Priego, Carlos, Saunders, Arven, Pan, Feng, Valdés, Víctor Julián, Kelley, Kevin, González Blanco, Miguel, Chen, Lingyi, Wang, Huayan, Sheng, Jia, Xu, Mingjiang, Fidalgo Pérez, Miguel Ángel, Shen, Xiaohua, Wang, Jianlong
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/45619
Acceso en línea:https://hdl.handle.net/10347/45619
Access Level:acceso abierto
Palabra clave:Epigenetics
TET2
RNA
Stem Cells
Investigación
Descripción
Sumario:Ten-eleven translocation (TET) proteins play key roles in the regulation of DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Unlike the other members of the TET family, TET2 does not contain a DNA-binding domain, and it remains unclear how it is recruited to chromatin. Here we show that TET2 is recruited by the RNA-binding protein Paraspeckle component 1 (PSPC1) through transcriptionally active loci, including endogenous retroviruses (ERVs) whose long terminal repeats (LTRs) have been co-opted by mammalian genomes as stage- and tissue-specific transcriptional regulatory modules. We found that PSPC1 and TET2 contribute to ERVL and ERVL-associated gene regulation by both transcriptional repression via histone deacetylases and post-transcriptional destabilization of RNAs through 5hmC modification. Our findings provide evidence for a functional role of transcriptionally active ERVs as specific docking sites for RNA epigenetic modulation and gene regulation

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