- Authors: Guallar, D., Bi, X., Pardavila, J. A., Huang, X., Saenz, C., Shi, X., Zhou, H., Faiola, F., Ding, J., Haruehanroengra, P., Yang, F., Li, D., Sanchez-Priego, C., Saunders, A., Pan, F., Valdes, V. J., Kelley, K., Blanco, M. G., Chen, L., Wang, H., Sheng, J., Xu, M., Fidalgo, M., Shen, X., Wang, J.
- Year: 2018
- Journal: Nat Genet 50 443-451
- Applications: in vitro / DNA / jetPRIME
- Cell type: Mouse embryonic stem cells
Description: Mouse stem cells derived from preimplantation-stage embryo.
Known as: mESCs
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.