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

Nature Genetics
Diana GuallarJianlong Wang

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.

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Datasets Mentioned

BETA
GSM611203
GSM611199
GSM1023124

Methods Mentioned

BETA
affinity purification
immunoprecipitation
coimmunoprecipitation
RNA-immunoprecipitation
pulldown
ChIP-seq
PCR
CLIP-seq
RNA-seq
affinity-purification

Software Mentioned

Bowtie
HTseq
SEQUEST
Bowtie2
Cufflinks
ImageJ
TopHat
len
DAVID
HOMER

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