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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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