Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation
The Xist lncRNA mediates X chromosome inactivation (XCI). Here we show that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen loss activates a subset of en...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54508 |
| _version_ | 1811199604471889920 |
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| author | Ava C Carter Jin Xu Meagan Y Nakamoto Yuning Wei Brian J Zarnegar Quanming Shi James P Broughton Ryan C Ransom Ankit Salhotra Surya D Nagaraja Rui Li Diana R Dou Kathryn E Yost Seung-Woo Cho Anil Mistry Michael T Longaker Paul A Khavari Robert T Batey Deborah S Wuttke Howard Y Chang |
| author_facet | Ava C Carter Jin Xu Meagan Y Nakamoto Yuning Wei Brian J Zarnegar Quanming Shi James P Broughton Ryan C Ransom Ankit Salhotra Surya D Nagaraja Rui Li Diana R Dou Kathryn E Yost Seung-Woo Cho Anil Mistry Michael T Longaker Paul A Khavari Robert T Batey Deborah S Wuttke Howard Y Chang |
| author_sort | Ava C Carter |
| collection | DOAJ |
| description | The Xist lncRNA mediates X chromosome inactivation (XCI). Here we show that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen loss activates a subset of endogenous retroviral (ERV) elements in mouse embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ERV RNA and Xist A-repeat bind the RRM domains of Spen in a competitive manner. Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in strictly local gene silencing in cis. These results suggest that Xist may coopt transposable element RNA-protein interactions to repurpose powerful antiviral chromatin silencing machinery for sex chromosome dosage compensation. |
| first_indexed | 2024-04-12T01:51:30Z |
| format | Article |
| id | doaj.art-4ae4315c8e724765a92613e02ab27e83 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:51:30Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4ae4315c8e724765a92613e02ab27e832022-12-22T03:52:56ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.54508Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivationAva C Carter0https://orcid.org/0000-0002-1892-8742Jin Xu1https://orcid.org/0000-0003-0944-9835Meagan Y Nakamoto2Yuning Wei3Brian J Zarnegar4Quanming Shi5James P Broughton6Ryan C Ransom7Ankit Salhotra8Surya D Nagaraja9Rui Li10Diana R Dou11https://orcid.org/0000-0001-6269-9636Kathryn E Yost12Seung-Woo Cho13Anil Mistry14Michael T Longaker15Paul A Khavari16Robert T Batey17Deborah S Wuttke18Howard Y Chang19https://orcid.org/0000-0002-9459-4393Center for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesDepartment of Biochemistry, University of Colorado, Boulder, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesDepartment of Dermatology, Stanford University School of Medicine, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, United StatesDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, United StatesInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United StatesNovartis Institute for Biomedical Research, Cambridge, United StatesDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, United States; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United StatesDepartment of Dermatology, Stanford University School of Medicine, Stanford, United StatesDepartment of Biochemistry, University of Colorado, Boulder, United StatesDepartment of Biochemistry, University of Colorado, Boulder, United StatesCenter for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United StatesThe Xist lncRNA mediates X chromosome inactivation (XCI). Here we show that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen loss activates a subset of endogenous retroviral (ERV) elements in mouse embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ERV RNA and Xist A-repeat bind the RRM domains of Spen in a competitive manner. Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in strictly local gene silencing in cis. These results suggest that Xist may coopt transposable element RNA-protein interactions to repurpose powerful antiviral chromatin silencing machinery for sex chromosome dosage compensation.https://elifesciences.org/articles/54508Xistlong noncoding RNAtransposonchromatinepigeneticgene silencing |
| spellingShingle | Ava C Carter Jin Xu Meagan Y Nakamoto Yuning Wei Brian J Zarnegar Quanming Shi James P Broughton Ryan C Ransom Ankit Salhotra Surya D Nagaraja Rui Li Diana R Dou Kathryn E Yost Seung-Woo Cho Anil Mistry Michael T Longaker Paul A Khavari Robert T Batey Deborah S Wuttke Howard Y Chang Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation eLife Xist long noncoding RNA transposon chromatin epigenetic gene silencing |
| title | Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation |
| title_full | Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation |
| title_fullStr | Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation |
| title_full_unstemmed | Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation |
| title_short | Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation |
| title_sort | spen links rna mediated endogenous retrovirus silencing and x chromosome inactivation |
| topic | Xist long noncoding RNA transposon chromatin epigenetic gene silencing |
| url | https://elifesciences.org/articles/54508 |
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