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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.740550/full |
| _version_ | 1818583200173129728 |
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| author | Thomas Rico Melissa Gilles Alban Chauderlier Thomas Comptdaer Romain Magnez Maggy Chwastyniak Herve Drobecq Florence Pinet Xavier Thuru Luc Buée Marie-Christine Galas Bruno Lefebvre |
| author_facet | Thomas Rico Melissa Gilles Alban Chauderlier Thomas Comptdaer Romain Magnez Maggy Chwastyniak Herve Drobecq Florence Pinet Xavier Thuru Luc Buée Marie-Christine Galas Bruno Lefebvre |
| author_sort | Thomas Rico |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T08:01:30Z |
| format | Article |
| id | doaj.art-779bd240c6244b8b8a4a3f6348dc3588 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T08:01:30Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-779bd240c6244b8b8a4a3f6348dc35882022-12-21T22:38:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.740550740550Tau Stabilizes Chromatin CompactionThomas Rico0Melissa Gilles1Alban Chauderlier2Thomas Comptdaer3Romain Magnez4Maggy Chwastyniak5Herve Drobecq6Florence Pinet7Xavier Thuru8Luc Buée9Marie-Christine Galas10Bruno Lefebvre11Univ. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, CNRS, INSERM, CHU Lille, UMR 9020, UMR 1277, Canther, Platform of Integrative Chemical Biology, Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, FranceUniv. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167 – RID-AGE – Facteurs de Risque et Déterminants Moléculaires des Maladies Liées Au Vieillissement, Lille, FranceUniv. Lille, CNRS UMR 9017, INSERM U1019, CHRU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, FranceUniv. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167 – RID-AGE – Facteurs de Risque et Déterminants Moléculaires des Maladies Liées Au Vieillissement, Lille, FranceUniv. Lille, CNRS, INSERM, CHU Lille, UMR 9020, UMR 1277, Canther, Platform of Integrative Chemical Biology, Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceUniv. Lille, INSERM, CHU-Lille, Lille Neuroscience and Cognition, UMR-S1172, Alzheimer and Tauopathies, Lille, FranceAn 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.740550/fullTau protein (Tau)chromatin remodelingchromatin regulationhistone modification and chromatin structurehistone deacetylase inhibitor (HDAC inhibitor)histone (de)acetylation |
| spellingShingle | Thomas Rico Melissa Gilles Alban Chauderlier Thomas Comptdaer Romain Magnez Maggy Chwastyniak Herve Drobecq Florence Pinet Xavier Thuru Luc Buée Marie-Christine Galas Bruno Lefebvre Tau Stabilizes Chromatin Compaction Frontiers in Cell and Developmental Biology Tau protein (Tau) chromatin remodeling chromatin regulation histone modification and chromatin structure histone deacetylase inhibitor (HDAC inhibitor) histone (de)acetylation |
| 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 | Tau protein (Tau) chromatin remodeling chromatin regulation histone modification and chromatin structure histone deacetylase inhibitor (HDAC inhibitor) histone (de)acetylation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.740550/full |
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