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Tau Stabilizes Chromatin Compaction
An extensive body of literature suggested a possible role of the microtubule-associated protein Tau in chromatin functions and/or organization in neuronal, non-neuronal, and cancer cells. How Tau functions in these processes remains elusive. Here we report that Tau expression in breast cancer cell l...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551707/ https://www.ncbi.nlm.nih.gov/pubmed/34722523 http://dx.doi.org/10.3389/fcell.2021.740550 |
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author | Rico, Thomas Gilles, Melissa Chauderlier, Alban Comptdaer, Thomas Magnez, Romain Chwastyniak, Maggy Drobecq, Herve Pinet, Florence Thuru, Xavier Buée, Luc Galas, Marie-Christine Lefebvre, Bruno |
author_facet | Rico, Thomas Gilles, Melissa Chauderlier, Alban Comptdaer, Thomas Magnez, Romain Chwastyniak, Maggy Drobecq, Herve Pinet, Florence Thuru, Xavier Buée, Luc Galas, Marie-Christine Lefebvre, Bruno |
author_sort | Rico, Thomas |
collection | PubMed |
description | An extensive body of literature suggested a possible role of the microtubule-associated protein Tau in chromatin functions and/or organization in neuronal, non-neuronal, and cancer cells. How Tau functions in these processes remains elusive. Here we report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects of histone deacetylase inhibitors, by preventing histone deacetylase inhibitor-inducible gene expression and remodeling of chromatin structure. We identify Tau as a protein recognizing and binding to core histone when H3 and H4 are devoid of any post-translational modifications or acetylated H4 that increases the Tau’s affinity. Consistent with chromatin structure alterations in neurons found in frontotemporal lobar degeneration, Tau mutations did not prevent histone deacetylase-inhibitor-induced higher chromatin structure remodeling by suppressing Tau binding to histones. In addition, we demonstrate that the interaction between Tau and histones prevents further histone H3 post-translational modifications induced by histone deacetylase-inhibitor treatment by maintaining a more compact chromatin structure. Altogether, these results highlight a new cellular role for Tau as a chromatin reader, which opens new therapeutic avenues to exploit Tau biology in neuronal and cancer cells. |
format | Online Article Text |
id | pubmed-8551707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85517072021-10-29 Tau Stabilizes Chromatin Compaction Rico, Thomas Gilles, Melissa Chauderlier, Alban Comptdaer, Thomas Magnez, Romain Chwastyniak, Maggy Drobecq, Herve Pinet, Florence Thuru, Xavier Buée, Luc Galas, Marie-Christine Lefebvre, Bruno Front Cell Dev Biol Cell and Developmental Biology An extensive body of literature suggested a possible role of the microtubule-associated protein Tau in chromatin functions and/or organization in neuronal, non-neuronal, and cancer cells. How Tau functions in these processes remains elusive. Here we report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects of histone deacetylase inhibitors, by preventing histone deacetylase inhibitor-inducible gene expression and remodeling of chromatin structure. We identify Tau as a protein recognizing and binding to core histone when H3 and H4 are devoid of any post-translational modifications or acetylated H4 that increases the Tau’s affinity. Consistent with chromatin structure alterations in neurons found in frontotemporal lobar degeneration, Tau mutations did not prevent histone deacetylase-inhibitor-induced higher chromatin structure remodeling by suppressing Tau binding to histones. In addition, we demonstrate that the interaction between Tau and histones prevents further histone H3 post-translational modifications induced by histone deacetylase-inhibitor treatment by maintaining a more compact chromatin structure. Altogether, these results highlight a new cellular role for Tau as a chromatin reader, which opens new therapeutic avenues to exploit Tau biology in neuronal and cancer cells. Frontiers Media S.A. 2021-10-14 /pmc/articles/PMC8551707/ /pubmed/34722523 http://dx.doi.org/10.3389/fcell.2021.740550 Text en Copyright © 2021 Rico, Gilles, Chauderlier, Comptdaer, Magnez, Chwastyniak, Drobecq, Pinet, Thuru, Buée, Galas and Lefebvre. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Rico, Thomas Gilles, Melissa Chauderlier, Alban Comptdaer, Thomas Magnez, Romain Chwastyniak, Maggy Drobecq, Herve Pinet, Florence Thuru, Xavier Buée, Luc Galas, Marie-Christine Lefebvre, Bruno Tau Stabilizes Chromatin Compaction |
title | Tau Stabilizes Chromatin Compaction |
title_full | Tau Stabilizes Chromatin Compaction |
title_fullStr | Tau Stabilizes Chromatin Compaction |
title_full_unstemmed | Tau Stabilizes Chromatin Compaction |
title_short | Tau Stabilizes Chromatin Compaction |
title_sort | tau stabilizes chromatin compaction |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551707/ https://www.ncbi.nlm.nih.gov/pubmed/34722523 http://dx.doi.org/10.3389/fcell.2021.740550 |
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