Frontiers in Cell and Developmental Biology (Oct 2021)

Tau Stabilizes Chromatin Compaction

  • 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

DOI
https://doi.org/10.3389/fcell.2021.740550
Journal volume & issue
Vol. 9

Abstract

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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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