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 Wang; Jia Sheng; Mingjiang Xu; Miguel Fidalgo; Xiaohua Shen; Jianlong Wang

doi:10.1038/s41588-018-0060-9

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 Wang

Jia Sheng, Mingjiang Xu, Miguel Fidalgo, Xiaohua Shen, Jianlong Wang

Chemistry

University at Albany

Icahn School of Medicine at Mount Sinai
Instituto de Investigación Sanitaria de Santiago de Compostela
Tsinghua University
Nankai University
SUNY Albany
Northwest Agriculture and Forestry University
University of Miami
Universidad Nacional Autónoma de México

Research output: Contribution to journal › Article › peer-review

148 Scopus citations

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 language	English
Pages (from-to)	443-451
Number of pages	9
Journal	Nature Genetics
Volume	50
Issue number	3
DOIs	https://doi.org/10.1038/s41588-018-0060-9
State	Published - Mar 1 2018

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Guallar, D., Bi, X., Pardavila, J. A., 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, V. J., Kelley, K., Blanco, M. G., Chen, L., ... Wang, J. (2018). RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature Genetics, 50(3), 443-451. https://doi.org/10.1038/s41588-018-0060-9

@article{33d8ac30887548f9988ffb2611087ba3,

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",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = mar,

day = "1",

doi = "10.1038/s41588-018-0060-9",

language = "English",

volume = "50",

pages = "443--451",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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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, vol. 50, no. 3, pp. 443-451. https://doi.org/10.1038/s41588-018-0060-9

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 - 2018/3/1

Y1 - 2018/3/1

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 - https://www.scopus.com/pages/publications/85042534855

U2 - 10.1038/s41588-018-0060-9

DO - 10.1038/s41588-018-0060-9

M3 - Article

C2 - 29483655

SN - 1061-4036

VL - 50

SP - 443

EP - 451

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

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