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

Authors :
Guallar D
Bi X
Pardavila JA
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 VJ
Kelley K
Blanco MG
Chen L
Wang H
Sheng J
Xu M
Fidalgo M
Shen X
Wang J
Source :
Nature genetics [Nat Genet] 2018 Mar; Vol. 50 (3), pp. 443-451. Date of Electronic Publication: 2018 Feb 26.
Publication Year :
2018

Abstract

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.

Details

Language :
English
ISSN :
1546-1718
Volume :
50
Issue :
3
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
29483655
Full Text :
https://doi.org/10.1038/s41588-018-0060-9