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

10 Oct 18

Speaker: Diana Guallar, PhD  - DNA Repair & Genome Integrity Lab – Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) – Campus Vida – Universidade de Santiago de Compostela – Spain



Organizers: IRB Barcelona

Date: Wednesday, 10 October, 13:00h

Place: Aula Fèlix Serratosa, Parc Científic de Barcelona

Host: Manuel Serrano, PhD



Ten-eleven translocation (TET) proteins play fundamental roles in regulating chromatin architecture and transcriptional events that define mammalian cellular identity but the molecular underpinnings that contribute to stable TET occupancy at the chromatin remain poorly understood. Here we demonstrate that TET2 is recruited to chromatin in an RNA-dependent manner through Paraspeckle component 1 (PSPC1) protein. By genome-wide analysis we show that PSPC1 binds both coding and non-coding RNAs including endogenous retroviruses (ERVs). Consistent with this PSPC1 depletion reduced TET2 binding to these abundant repetitive sequences and resulted in transcriptional deregulation of these parasitic mammalian elements. Notably we discovered that early embryonic MERVL endogenous retrovirus expression is tightly regulated by dual TET2 independent functions: transcriptional repression via histone deacetylation and RNA destabilization via 5-hydroxymethylcytosine (5hmC) deposition. Our findings reveal a critical role for an RNA modulation of TET2 function at the chromatin level and provide evidences for a functional role of 5hmC RNA modification in posttranscriptional regulation of endogenous retroviruses.


Molecular Medicine Programme Seminar