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

Diana Guallar, Xianju Bi, Jose Angel Pardavila, Xin Huang, Carmen Saenz, Xianle Shi, Hongwei Zhou, Francesco Faiola, Junjun Ding, Phensinee Haruehanroengra, Fan Yang, Dan Li, Carlos Sanchez-Priego, Arven Saunders, Feng Pan, Victor Julian Valdes, Kevin Kelley, Miguel G. Blanco, Lingyi Chen, Huayan WangJia Sheng, Mingjiang Xu, Miguel Fidalgo, Xiaohua Shen, Jianlong Wang

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalNature Genetics
DOIs
StateAccepted/In press - Feb 26 2018

Fingerprint

Endogenous Retroviruses
Pluripotent Stem Cells
Epigenomics
Chromatin
RNA
5-Methylcytosine
Histone Deacetylases
RNA-Binding Proteins
Terminal Repeat Sequences
Protein Transport
DNA Methylation
Genes
Genome
DNA
5-hydroxymethylcytosine

ASJC Scopus subject areas

  • Genetics

Cite this

Guallar, D., Bi, X., Pardavila, J. A., Huang, X., Saenz, C., Shi, X., ... Wang, J. (Accepted/In press). RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature Genetics, 1-9. https://doi.org/10.1038/s41588-018-0060-9

RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. / Guallar, Diana; Bi, Xianju; Pardavila, Jose Angel; Huang, Xin; Saenz, Carmen; Shi, Xianle; Zhou, Hongwei; Faiola, Francesco; Ding, Junjun; Haruehanroengra, Phensinee; Yang, Fan; Li, Dan; Sanchez-Priego, Carlos; Saunders, Arven; Pan, Feng; Valdes, Victor Julian; Kelley, Kevin; Blanco, Miguel G.; Chen, Lingyi; Wang, Huayan; Sheng, Jia; Xu, Mingjiang; Fidalgo, Miguel; Shen, Xiaohua; Wang, Jianlong.

In: Nature Genetics, 26.02.2018, p. 1-9.

Research output: Contribution to journalArticle

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 2018, 'RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells', Nature Genetics, pp. 1-9. https://doi.org/10.1038/s41588-018-0060-9
Guallar, Diana ; Bi, Xianju ; Pardavila, Jose Angel ; Huang, Xin ; Saenz, Carmen ; Shi, Xianle ; Zhou, Hongwei ; Faiola, Francesco ; Ding, Junjun ; Haruehanroengra, Phensinee ; Yang, Fan ; Li, Dan ; Sanchez-Priego, Carlos ; Saunders, Arven ; Pan, Feng ; Valdes, Victor Julian ; Kelley, Kevin ; Blanco, Miguel G. ; Chen, Lingyi ; Wang, Huayan ; Sheng, Jia ; Xu, Mingjiang ; Fidalgo, Miguel ; Shen, Xiaohua ; Wang, Jianlong. / RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. In: Nature Genetics. 2018 ; pp. 1-9.
@article{1d325539a2e848f19250129585866545,
title = "RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells",
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.",
author = "Diana Guallar and Xianju Bi and Pardavila, {Jose Angel} and Xin Huang and Carmen Saenz and Xianle Shi and Hongwei Zhou and Francesco Faiola and Junjun Ding and Phensinee Haruehanroengra and Fan Yang and Dan Li and Carlos Sanchez-Priego and Arven Saunders and Feng Pan and Valdes, {Victor Julian} and Kevin Kelley and Blanco, {Miguel G.} and Lingyi Chen and Huayan Wang and Jia Sheng and Mingjiang Xu and Miguel Fidalgo and Xiaohua Shen and Jianlong Wang",
year = "2018",
month = "2",
day = "26",
doi = "10.1038/s41588-018-0060-9",
language = "English (US)",
pages = "1--9",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells

AU - Guallar, Diana

AU - Bi, Xianju

AU - Pardavila, Jose Angel

AU - Huang, Xin

AU - Saenz, Carmen

AU - Shi, Xianle

AU - Zhou, Hongwei

AU - Faiola, Francesco

AU - Ding, Junjun

AU - Haruehanroengra, Phensinee

AU - Yang, Fan

AU - Li, Dan

AU - Sanchez-Priego, Carlos

AU - Saunders, Arven

AU - Pan, Feng

AU - Valdes, Victor Julian

AU - Kelley, Kevin

AU - Blanco, Miguel G.

AU - Chen, Lingyi

AU - Wang, Huayan

AU - Sheng, Jia

AU - Xu, Mingjiang

AU - Fidalgo, Miguel

AU - Shen, Xiaohua

AU - Wang, Jianlong

PY - 2018/2/26

Y1 - 2018/2/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85042534855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042534855&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0060-9

DO - 10.1038/s41588-018-0060-9

M3 - Article

C2 - 29483655

AN - SCOPUS:85042534855

SP - 1

EP - 9

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -