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

iScience. 2022 Jul 20;25(8):104796. doi: 10.1016/j.isci.2022.104796. eCollection 2022 Aug 19.

Authors

Alexander J Moorhouse¹, Amy E Loats¹, Kathryn F Medler², Stefan G E Roberts^{1

2}

Affiliations

¹ School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
² Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA.

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.

Keywords: Molecular Genetics; Molecular biology; Omics; Transcriptomics.

Abstract

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