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The LINC Complex Inhibits Excessive Chromatin Repression

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in...

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Autores principales: Amiad Pavlov, Daria, Unnikannan, CP, Lorber, Dana, Bajpai, Gaurav, Olender, Tsviya, Stoops, Elizabeth, Reuveny, Adriana, Safran, Samuel, Volk, Talila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047284/
https://www.ncbi.nlm.nih.gov/pubmed/36980273
http://dx.doi.org/10.3390/cells12060932
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author Amiad Pavlov, Daria
Unnikannan, CP
Lorber, Dana
Bajpai, Gaurav
Olender, Tsviya
Stoops, Elizabeth
Reuveny, Adriana
Safran, Samuel
Volk, Talila
author_facet Amiad Pavlov, Daria
Unnikannan, CP
Lorber, Dana
Bajpai, Gaurav
Olender, Tsviya
Stoops, Elizabeth
Reuveny, Adriana
Safran, Samuel
Volk, Talila
author_sort Amiad Pavlov, Daria
collection PubMed
description The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, where the nuclei are exposed to significant mechanical inputs during muscle contraction. To this end, the genomic binding profiles of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex. A significant increase in the binding of Polycomb and parallel reduction of RNA-Pol-II binding to a set of muscle genes was observed. Consistently, enhanced tri-methylated H3K9 and H3K27 repressive modifications and reduced chromatin activation by H3K9 acetylation were found. Furthermore, larger tri-methylated H3K27me3 repressive clusters, and chromatin redistribution from the nuclear periphery towards nuclear center, were detected in live LINC mutant larval muscles. Computer simulation indicated that the observed dissociation of the chromatin from the nuclear envelope promotes growth of tri-methylated H3K27 repressive clusters. Thus, we suggest that by promoting chromatin–nuclear envelope binding, the LINC complex restricts the size of repressive H3K27 tri-methylated clusters, thereby limiting the binding of Polycomb transcription repressor, directing robust transcription in muscle fibers.
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spelling pubmed-100472842023-03-29 The LINC Complex Inhibits Excessive Chromatin Repression Amiad Pavlov, Daria Unnikannan, CP Lorber, Dana Bajpai, Gaurav Olender, Tsviya Stoops, Elizabeth Reuveny, Adriana Safran, Samuel Volk, Talila Cells Article The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, where the nuclei are exposed to significant mechanical inputs during muscle contraction. To this end, the genomic binding profiles of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex. A significant increase in the binding of Polycomb and parallel reduction of RNA-Pol-II binding to a set of muscle genes was observed. Consistently, enhanced tri-methylated H3K9 and H3K27 repressive modifications and reduced chromatin activation by H3K9 acetylation were found. Furthermore, larger tri-methylated H3K27me3 repressive clusters, and chromatin redistribution from the nuclear periphery towards nuclear center, were detected in live LINC mutant larval muscles. Computer simulation indicated that the observed dissociation of the chromatin from the nuclear envelope promotes growth of tri-methylated H3K27 repressive clusters. Thus, we suggest that by promoting chromatin–nuclear envelope binding, the LINC complex restricts the size of repressive H3K27 tri-methylated clusters, thereby limiting the binding of Polycomb transcription repressor, directing robust transcription in muscle fibers. MDPI 2023-03-18 /pmc/articles/PMC10047284/ /pubmed/36980273 http://dx.doi.org/10.3390/cells12060932 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Amiad Pavlov, Daria
Unnikannan, CP
Lorber, Dana
Bajpai, Gaurav
Olender, Tsviya
Stoops, Elizabeth
Reuveny, Adriana
Safran, Samuel
Volk, Talila
The LINC Complex Inhibits Excessive Chromatin Repression
title The LINC Complex Inhibits Excessive Chromatin Repression
title_full The LINC Complex Inhibits Excessive Chromatin Repression
title_fullStr The LINC Complex Inhibits Excessive Chromatin Repression
title_full_unstemmed The LINC Complex Inhibits Excessive Chromatin Repression
title_short The LINC Complex Inhibits Excessive Chromatin Repression
title_sort linc complex inhibits excessive chromatin repression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047284/
https://www.ncbi.nlm.nih.gov/pubmed/36980273
http://dx.doi.org/10.3390/cells12060932
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