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RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells.
- 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.
- Subjects :
- Animals
Cells, Cultured
Chromatin genetics
DNA Methylation
Dioxygenases
Epigenesis, Genetic physiology
Female
HEK293 Cells
Humans
Male
Mice
Protein Binding
Chromatin metabolism
DNA-Binding Proteins metabolism
Endogenous Retroviruses physiology
Nuclear Proteins metabolism
Pluripotent Stem Cells metabolism
Proto-Oncogene Proteins metabolism
RNA physiology
RNA-Binding Proteins metabolism
Subjects
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