AI Article Synopsis

  • TET proteins, particularly TET2, are crucial for regulating DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine, impacting gene expression.
  • Unlike other TET proteins, TET2 lacks a DNA-binding domain, and its recruitment to chromatin is facilitated by the RNA-binding protein PSPC1, especially at transcriptionally active regions like endogenous retroviruses (ERVs).
  • The collaboration between PSPC1 and TET2 supports gene regulation by repressing transcription through histone deacetylation and destabilizing RNAs via 5hmC modifications, highlighting the role of ERVs in epigenetic modulation.

Article 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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862756PMC
http://dx.doi.org/10.1038/s41588-018-0060-9DOI Listing

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