Tau Stabilizes Chromatin Compaction.

Abstract

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.

• Authors: 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
• Journal: Frontiers in cell and developmental biology (Front Cell Dev Biol) Vol. 9 Pg. 740550 ( 2021) ISSN: 2296-634X [Print] Switzerland
• PMID: 34722523 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Rico, Gilles, Chauderlier, Comptdaer, Magnez, Chwastyniak, Drobecq, Pinet, Thuru, Buée, Galas and Lefebvre.