Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity

Dominique Ray-Gallet (1) , Adam Woolfe (1) , Isabelle Vassias (2) , Céline Pellentz (3) , Nicolas Lacoste (1) , Aastha Puri (4) , David C Schultz (5) , Nikolay A Pchelintsev (6) , Peter D Adams (6) , Lars E T Jansen (7) , Geneviève Almouzni (1)

1 DNPG - Dynamique nucléaire et plasticité du génome
2 LNRS - Laboratoire de Neurobiologie des Réseaux Sensorimoteurs
3 LMARG - Laboratoire du Métabolisme de l'ADN et Réponses aux Génotoxiques
4 The Wistar Institute
5 The Wistar Institute
6 The Beatson Institute for Cancer Research
7 IGC - Instituto Gulbenkian de Ciência [Oeiras]

Establishment of a proper chromatin landscape is central to genome function. Here, we explain H3 variant distribution by specific targeting and dynamics of deposition involving the CAF-1 and HIRA histone chaperones. Impairing replicative H3.1 incorporation via CAF-1 enables an alternative H3.3 deposition at replication sites via HIRA. Conversely, the H3.3 incorporation throughout the cell cycle via HIRA cannot be replaced by H3.1. ChIP-seq analyses reveal correlation between HIRA-dependent H3.3 accumulation and RNA pol II at transcription sites and specific regulatory elements, further supported by their biochemical association. The HIRA complex shows unique DNA binding properties, and depletion of HIRA increases DNA sensitivity to nucleases. We propose that protective nucleosome gap filling of naked DNA by HIRA leads to a broad distribution of H3.3, and HIRA association with Pol II ensures local H3.3 enrichment at specific sites. We discuss the importance of this H3.3 deposition as a salvage pathway to maintain chromatin integrity.

Domaines: Biologie cellulaire

Dominique Ray-Gallet, Adam Woolfe, Isabelle Vassias, Céline Pellentz, Nicolas Lacoste, et al.. Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity. Molecular Cell, 2011, 44 (6), pp.928-41. ⟨10.1016/j.molcel.2011.12.006⟩. ⟨hal-00743096⟩