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The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms
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 acti...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379585/ https://www.ncbi.nlm.nih.gov/pubmed/35982799 http://dx.doi.org/10.1016/j.isci.2022.104796 |
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author | Moorhouse, Alexander J. Loats, Amy E. Medler, Kathryn F. Roberts, Stefan G.E. |
author_facet | Moorhouse, Alexander J. Loats, Amy E. Medler, Kathryn F. Roberts, Stefan G.E. |
author_sort | Moorhouse, Alexander J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9379585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-93795852022-08-17 The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms Moorhouse, Alexander J. Loats, Amy E. Medler, Kathryn F. Roberts, Stefan G.E. iScience Article 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. Elsevier 2022-07-20 /pmc/articles/PMC9379585/ /pubmed/35982799 http://dx.doi.org/10.1016/j.isci.2022.104796 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Moorhouse, Alexander J. Loats, Amy E. Medler, Kathryn F. Roberts, Stefan G.E. The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379585/ https://www.ncbi.nlm.nih.gov/pubmed/35982799 http://dx.doi.org/10.1016/j.isci.2022.104796 |
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