Tau Stabilizes Chromatin Compaction.
Thomas Rico,Melissa Gilles,Alban Chauderlier,Thomas Comptdaer,Romain Magnez,Maggy Chwastyniak,Hervé Drobecq,Florence Pinet,Xavier Thuru,Luc Buée,Marie-Christine Galas,Bruno Lefebvre +11 more
Reads0
Chats0
TLDR
In this paper, the microtubule-associated protein Tau was identified 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.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.read more
Citations
More filters
Posted ContentDOI
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies
Marco Antônio De Bastiani,Bruna Bellaver,Wagner Scheeren Brum,Débora Guerini Souza,Pâmela C. Lukasewicz Ferreira,Andreia Silva da Rocha,Guilherme Povala,J. P. Ferrari-Souza,Andrea Lessa Benedet,Nicholas J. Ashton,Thomas K. Karikari,Henrik Zetterberg,Kaj Blennow,Pedro Rosa-Neto,Tharick A. Pascoal,Eduardo R. Zimmer +15 more
TL;DR: This study revealed molecular signatures driven by AD hallmarks in hippocampal GFAP-positive astrocytes, including a scarce overlap of differentially expressed genes (DEG) driven by Aβ and tau; abnormalities in proteostasis and exocytosis-related processes in Aβ-driven reactive astroCytes and impaired DNA/RNA processing and cytoskeleton dynamics in tau-driven astroicytes.
Journal ArticleDOI
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies
TL;DR: In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis as mentioned in this paper .
Journal ArticleDOI
Pathological Nuclear Hallmarks in Dentate Granule Cells of Alzheimer’s Patients: A Biphasic Regulation of Neurogenesis
Laura Gil,Erika Chi-Ahumada,Sandra A. Niño,Gabriela Capdeville,Areli M. Méndez-Torres,Carmen Guerrero,Ana Belén Rebolledo,Isabel M. Olazabal,María E. Jiménez-Capdeville +8 more
TL;DR: Late AD stages, the progressive disappearance of phosphorylated Tau forms in the nucleus, increased chromatin disorganization, and increased nuclear autophagy support a model of biphasic neurogenesis in AD, which might be the only pathway to a true rejuvenation of brain circuits.
Journal ArticleDOI
Tau-dependent HDAC1 nuclear reduction is associated with altered VGluT1 expression
Giacomo Siano,Giuseppe Madaro,Maria Claudia Caiazza,Awatef Allouch,Marianna Mignanelli,Antonino Cattaneo,Cristina Di Primio +6 more
TL;DR: In this article , the authors investigated the relationship between Tau and these epigenetic factors, and they demonstrated that Tau altered expression in the neuronal cell line SH-SY5y does not alter TRIM28 and HDAC1 expression but it induces a subcellular reduction of HAC1 in the nuclear compartment.
Posted ContentDOI
Tau Protein Modulates an Epigenetic Mechanism of Cellular Senescence
Claudia Magrin,Martín E García Solá,Ester Piovesana,Marco Bolis,Andrea Rinaldi,Stéphanie Papin,Paolo Paganetti +6 more
TL;DR: In this paper , a bioinformatics analysis of transcriptome data obtained from Tau-depleted human neuroblastoma cells was performed to better characterize the possible role of Tau in regulation of chromatin compaction and subsequent gene expression.
References
More filters
Journal ArticleDOI
Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions
Michael Shogren-Knaak,Haruhiko Ishii,Jian-Min Sun,Michael J. Pazin,James R. Davie,Craig L. Peterson +5 more
TL;DR: H4-K16Ac inhibits the ability of the adenosine triphosphate–utilizing chromatin assembly and remodeling enzyme ACF to mobilize a mononucleosome, indicating that this single histone modification modulates both higher order chromatin structure and functional interactions between a nonhistone protein and the chromatin fiber.
Journal ArticleDOI
The molecular hallmarks of epigenetic control
C. David Allis,Thomas Jenuwein +1 more
TL;DR: A personal perspective on the development of epigenetics, from its historical origins to what is defined as 'the modern era of epigenetic research', is provided.
Journal ArticleDOI
Tau in physiology and pathology
Yipeng Wang,Eckhard Mandelkow +1 more
TL;DR: The expression, post-translational modifications and functions of tau in physiology and in pathophysiology are reviewed, including the identification of new physiological roles for t Tau in the brain.
Journal ArticleDOI
Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation.
TL;DR: The present findings indicate that the induction of p21(WAF1) by SAHA is regulated, at least in part, by the degree of acetylation of the gene-associated histones and that this induced increase in acetylations is gene selective.
Journal ArticleDOI
Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase.
Stefan Kubicek,Roderick J. O'Sullivan,E. Michael August,Eugene R. Hickey,Qiang Zhang,Miguel L L. Teodoro,Stephen Rea,Karl Mechtler,Jennifer A. Kowalski,Carol Ann Homon,Terence A. Kelly,Thomas Jenuwein +11 more
TL;DR: In this article, the authors identify a biologically active HMTase inhibitor that allows for the transient modulation of H3K9me2 marks in mammalian chromatin and demonstrate that transient incubation of several cell lines with BIX-01294 lowers bulk H3 K 9me2 levels that are restored upon removal of the inhibitor.