The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
TLDR
The data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3, establishing a new link between the PML bodies and the regulation of pericentric DNA repeat chromatin structure.Abstract:
The histone variant H3.3 marks active chromatin by replacing the conventional histone H3.1. In this study, we investigate the detailed mechanism of H3.3 replication-independent deposition. We found that the death domain-associated protein DAXX and the chromatin remodeling factor ATRX (α-thalassemia/mental retardation syndrome protein) are specifically associated with the H3.3 deposition machinery. Bacterially expressed DAXX has a marked binding preference for H3.3 and assists the deposition of (H3.3–H4)2 tetramers on naked DNA, thus showing that DAXX is a H3.3 histone chaperone. In DAXX-depleted cells, a fraction of H3.3 was found associated with the replication-dependent machinery of deposition, suggesting that cells adapt to the depletion. The reintroduced DAXX in these cells colocalizes with H3.3 into the promyelocytic leukemia protein (PML) bodies. Moreover, DAXX associates with pericentric DNA repeats, and modulates the transcription from these repeats through assembly of H3.3 nucleosomes. These findings establish a new link between the PML bodies and the regulation of pericentric DNA repeat chromatin structure. Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3.read more
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Histone methylation: a dynamic mark in health, disease and inheritance
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TL;DR: This work provides a broad overview of how histone methylation is regulated and leads to biological outcomes and suggests its links to disease and ageing and possibly to transmission of traits across generations are illustrated.
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Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.
Dominik Sturm,Hendrik Witt,Hendrik Witt,Volker Hovestadt,Dong Anh Khuong-Quang,David T.W. Jones,Carolin Konermann,Elke Pfaff,Martje Tönjes,Martin Sill,Sebastian Bender,Marcel Kool,Marc Zapatka,Natalia Becker,Manuela Zucknick,Thomas Hielscher,Xiaoyang Liu,Adam M. Fontebasso,Marina Ryzhova,Steffen Albrecht,Karine Jacob,Marietta Wolter,Martin Ebinger,Martin U. Schuhmann,Timothy E. Van Meter,Michael C. Frühwald,Holger Hauch,Arnulf Pekrun,Bernhard Radlwimmer,Tim Niehues,Gregor Von Komorowski,Matthias Dürken,Andreas E. Kulozik,Jenny Madden,Andrew M. Donson,Nicholas K. Foreman,Rachid Drissi,Maryam Fouladi,Wolfram Scheurlen,Andreas von Deimling,Andreas von Deimling,Camelia M. Monoranu,Wolfgang Roggendorf,Christel Herold-Mende,Andreas Unterberg,Christof M. Kramm,Jörg Felsberg,Christian Hartmann,Benedikt Wiestler,Wolfgang Wick,Till Milde,Till Milde,Olaf Witt,Olaf Witt,Anders Lindroth,Jeremy Schwartzentruber,Damien Faury,Adam Fleming,Magdalena Zakrzewska,Pawel P. Liberski,Krzysztof Zakrzewski,Peter Hauser,Miklós Garami,Almos Klekner,László Bognár,Sorana Morrissy,Florence M.G. Cavalli,Michael D. Taylor,Peter van Sluis,Jan Koster,Rogier Versteeg,Richard Volckmann,Tom Mikkelsen,Kenneth Aldape,Guido Reifenberger,V. Peter Collins,Jacek Majewski,Andrey Korshunov,Peter Lichter,Christoph Plass,Nada Jabado,Stefan M. Pfister,Stefan M. Pfister +82 more
TL;DR: It is demonstrated that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup.
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Daxx/atrx, men1, and mtor pathway genes are frequently altered in pancreatic neuroendocrine tumors
Yuchen Jiao,Chanjuan Shi,Barish H. Edil,Roeland F. de Wilde,David S. Klimstra,Anirban Maitra,Richard D. Schulick,Laura H. Tang,Christopher L. Wolfgang,Michael A. Choti,Victor E. Velculescu,Luis A. Diaz,Bert Vogelstein,Kenneth W. Kinzler,Ralph H. Hruban,Nickolas Papadopoulos +15 more
TL;DR: Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis and a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors was found.
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Enhancer function: new insights into the regulation of tissue-specific gene expression.
Chin-Tong Ong,Victor G. Corces +1 more
TL;DR: Surprisingly, cohesin and non-coding RNAs are emerging as crucial players responsible for facilitating enhancer–promoter interactions at some genes and may be required not only to facilitate initiation of transcription but also to activate the release of RNA polymerase II from promoter-proximal pausing.
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Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
TL;DR: It is found that the ATRX–Daxx complex is bound to telomeric chromatin, and that both components of this complex are required for H3.3 deposition at telomeres in murine embryonic stem cells (ESCs).
References
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