The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms

Alexander J Moorhouse; Amy E Loats; Kathryn F Medler; Stefan G E Roberts

doi:10.1016/j.isci.2022.104796

The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms

Alexander J Moorhouse, Amy E Loats, Kathryn F Medler, Stefan G E Roberts

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

5 Citations (SciVal)

Abstract

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.

Original language	English
Article number	104796
Pages (from-to)	104796
Journal	iScience
Volume	25
Issue number	8
DOIs	https://doi.org/10.1016/j.isci.2022.104796
Publication status	Published - 19 Aug 2022

Bibliographical note

Funding Information:
This work was funded by the BBSRC so SGER ( BB/T001925/1 ) and NIH to KFM and SGER ( 1R01GM098609 ). AEL was supported by a Wellcome Trust PhD Studentship for the Dynamic Cell Biology program ( 083474 ). Would like to thank Mutia Muna for her help with the BASP1 mouse experiments.

Funding Information:
This work was funded by the BBSRC so SGER (BB/T001925/1) and NIH to KFM and SGER (1R01GM098609). AEL was supported by a Wellcome Trust PhD Studentship for the Dynamic Cell Biology program (083474). Would like to thank Mutia Muna for her help with the BASP1 mouse experiments. The study was conceptualized and designed by AJM, AEL, KFM, and SGER. All authors performed experiments and analyzed the data. AJM and SGER wrote the article. All authors discussed the results from the experiments and commented on the article. SGER supervised the project. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.

Publisher Copyright:
© 2022 The Author(s)

Keywords

Molecular Genetics
Molecular biology
Omics
Transcriptomics

ASJC Scopus subject areas

General

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10.1016/j.isci.2022.104796Licence: CC BY

Cite this

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title = "The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms",

abstract = "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.",

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note = "Funding Information: This work was funded by the BBSRC so SGER ( BB/T001925/1 ) and NIH to KFM and SGER ( 1R01GM098609 ). AEL was supported by a Wellcome Trust PhD Studentship for the Dynamic Cell Biology program ( 083474 ). Would like to thank Mutia Muna for her help with the BASP1 mouse experiments. Funding Information: This work was funded by the BBSRC so SGER (BB/T001925/1) and NIH to KFM and SGER (1R01GM098609). AEL was supported by a Wellcome Trust PhD Studentship for the Dynamic Cell Biology program (083474). Would like to thank Mutia Muna for her help with the BASP1 mouse experiments. The study was conceptualized and designed by AJM, AEL, KFM, and SGER. All authors performed experiments and analyzed the data. AJM and SGER wrote the article. All authors discussed the results from the experiments and commented on the article. SGER supervised the project. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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N2 - 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.

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The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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