The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms
Summary: The transcriptional corepressor BASP1 requires N-terminal myristoylation for its activity and functions through interactions with nuclear lipids. Here we determine the role of BASP1 lipidation in histone modification and the modulation of chromatin accessibility. We find that the removal of...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222010689 |
| _version_ | 1798041118769676288 |
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| author | Alexander J. Moorhouse Amy E. Loats Kathryn F. Medler Stefan G.E. Roberts |
| author_facet | Alexander J. Moorhouse Amy E. Loats Kathryn F. Medler Stefan G.E. Roberts |
| author_sort | Alexander J. Moorhouse |
| collection | DOAJ |
| description | Summary: The transcriptional corepressor BASP1 requires N-terminal myristoylation for its activity and functions through interactions with nuclear lipids. Here we determine the role of BASP1 lipidation in histone modification and the modulation of chromatin accessibility. We find that the removal of the active histone modifications H3K9ac and H3K4me3 by BASP1 requires the N-terminal myristoylation of BASP1. In contrast, the placement of the repressive histone modification, H3K27me3, by BASP1 does not require BASP1 lipidation. RNA-seq and ATAC-seq analysis finds that BASP1 regulates the activity of multiple transcription factors and induces extensive changes in chromatin accessibility. We find that ∼50% of BASP1 target genes show lipidation-dependent chromatin compaction and transcriptional repression. Our results suggest that BASP1 elicits both lipid-dependent and lipid-independent functions in histone modification and transcriptional repression. In accordance with this, we find that the tumor suppressor activity of BASP1 is also partially dependent on its myristoylation. |
| first_indexed | 2024-04-11T22:17:02Z |
| format | Article |
| id | doaj.art-33f7b2143b3442deb9ca641f850b4e4f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T22:17:02Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-33f7b2143b3442deb9ca641f850b4e4f2022-12-22T04:00:21ZengElsevieriScience2589-00422022-08-01258104796The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanismsAlexander J. Moorhouse0Amy E. Loats1Kathryn F. Medler2Stefan G.E. Roberts3School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UKSchool of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UKDepartment of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USASchool of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA; Corresponding authorSummary: The transcriptional corepressor BASP1 requires N-terminal myristoylation for its activity and functions through interactions with nuclear lipids. Here we determine the role of BASP1 lipidation in histone modification and the modulation of chromatin accessibility. We find that the removal of the active histone modifications H3K9ac and H3K4me3 by BASP1 requires the N-terminal myristoylation of BASP1. In contrast, the placement of the repressive histone modification, H3K27me3, by BASP1 does not require BASP1 lipidation. RNA-seq and ATAC-seq analysis finds that BASP1 regulates the activity of multiple transcription factors and induces extensive changes in chromatin accessibility. We find that ∼50% of BASP1 target genes show lipidation-dependent chromatin compaction and transcriptional repression. Our results suggest that BASP1 elicits both lipid-dependent and lipid-independent functions in histone modification and transcriptional repression. In accordance with this, we find that the tumor suppressor activity of BASP1 is also partially dependent on its myristoylation.http://www.sciencedirect.com/science/article/pii/S2589004222010689Molecular biologyMolecular GeneticsOmicsTranscriptomics |
| spellingShingle | Alexander J. Moorhouse Amy E. Loats Kathryn F. Medler Stefan G.E. Roberts The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms iScience Molecular biology Molecular Genetics Omics Transcriptomics |
| title | The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
| title_full | The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
| title_fullStr | The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
| title_full_unstemmed | The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
| title_short | The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
| title_sort | basp1 transcriptional corepressor modifies chromatin through lipid dependent and lipid independent mechanisms |
| topic | Molecular biology Molecular Genetics Omics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222010689 |
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