The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3

Pascal Drané, Khalid Ouararhni, Arnaud Depaux, Muhammad Shuaib, Ali Hamiche

Research output: Contribution to journalArticle

355 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1253-1265
Number of pages13
JournalGenes and Development
Volume24
Issue number12
DOIs
Publication statusPublished - 15 Jun 2010
Externally publishedYes

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Keywords

  • H3.3
  • Histone chaperone
  • Histone variant
  • PML-NBs

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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