The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs
Summary: Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422030938X |
| _version_ | 1818341428645855232 |
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| author | Guifeng Wei Neil Brockdorff Tianyi Zhang |
| author_facet | Guifeng Wei Neil Brockdorff Tianyi Zhang |
| author_sort | Guifeng Wei |
| collection | DOAJ |
| description | Summary: Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans. |
| first_indexed | 2024-12-13T15:58:38Z |
| format | Article |
| id | doaj.art-a018d1b1e063427d8727a4e6c17a474f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-13T15:58:38Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-a018d1b1e063427d8727a4e6c17a474f2022-12-21T23:39:15ZengElsevieriScience2589-00422020-11-012311101741The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCsGuifeng Wei0Neil Brockdorff1Tianyi Zhang2Development Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKDevelopment Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Corresponding authorDevelopment Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Lymphocyte Development and Single Molecule Imaging, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK; Corresponding authorSummary: Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans.http://www.sciencedirect.com/science/article/pii/S258900422030938XMolecular BiologyMolecular Mechanism of Gene RegulationStem Cells Research |
| spellingShingle | Guifeng Wei Neil Brockdorff Tianyi Zhang The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs iScience Molecular Biology Molecular Mechanism of Gene Regulation Stem Cells Research |
| title | The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs |
| title_full | The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs |
| title_fullStr | The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs |
| title_full_unstemmed | The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs |
| title_short | The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs |
| title_sort | pwwp2a histone deacetylase complex represses intragenic spurious transcription initiation in mescs |
| topic | Molecular Biology Molecular Mechanism of Gene Regulation Stem Cells Research |
| url | http://www.sciencedirect.com/science/article/pii/S258900422030938X |
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