Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation
<p>Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and their relationship with one another is poorly understo...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2019
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| _version_ | 1826305574211420160 |
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| author | Nesterova, TB Wei, G Coker, H Pintacuda, G Bowness, JS Zhang, T Almeida, M Bloechl, B Moindrot, B Carter, EJ Rodrigo, I Pan, Q Bi, Y Song, C-X Brockdorff, N |
| author_facet | Nesterova, TB Wei, G Coker, H Pintacuda, G Bowness, JS Zhang, T Almeida, M Bloechl, B Moindrot, B Carter, EJ Rodrigo, I Pan, Q Bi, Y Song, C-X Brockdorff, N |
| author_sort | Nesterova, TB |
| collection | OXFORD |
| description | <p>Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in mouse embryonic stem cell-based models. Using a machine learning approach we identify distance to the <em>Xist</em>locus and prior gene expression levels as key determinants of silencing efficiency. We go on to show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/m6A-methyltransferase complex make only minor contributions to gene silencing. Together our results provide a comprehensive model for Xist-mediated chromosome silencing.</p> |
| first_indexed | 2024-03-07T06:34:54Z |
| format | Journal article |
| id | oxford-uuid:f741998a-b2d8-4d79-8583-91bc680b3d66 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:34:54Z |
| publishDate | 2019 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:f741998a-b2d8-4d79-8583-91bc680b3d662022-03-27T12:41:39ZSystematic allelic analysis defines the interplay of key pathways in X chromosome inactivationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f741998a-b2d8-4d79-8583-91bc680b3d66EnglishSymplectic Elements at OxfordSpringer2019Nesterova, TBWei, GCoker, HPintacuda, GBowness, JSZhang, TAlmeida, MBloechl, BMoindrot, BCarter, EJRodrigo, IPan, QBi, YSong, C-XBrockdorff, N<p>Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in mouse embryonic stem cell-based models. Using a machine learning approach we identify distance to the <em>Xist</em>locus and prior gene expression levels as key determinants of silencing efficiency. We go on to show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/m6A-methyltransferase complex make only minor contributions to gene silencing. Together our results provide a comprehensive model for Xist-mediated chromosome silencing.</p> |
| spellingShingle | Nesterova, TB Wei, G Coker, H Pintacuda, G Bowness, JS Zhang, T Almeida, M Bloechl, B Moindrot, B Carter, EJ Rodrigo, I Pan, Q Bi, Y Song, C-X Brockdorff, N Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title | Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title_full | Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title_fullStr | Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title_full_unstemmed | Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title_short | Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation |
| title_sort | systematic allelic analysis defines the interplay of key pathways in x chromosome inactivation |
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