title: Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity.
abstract: 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.
authors.affiliation: Centre de Recherche, Institut Curie, 75248 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Ray-Gallet
authors.forename: Adam
authors.initials: A
authors.lastname: Woolfe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vassias
authors.forename: Céline
authors.initials: C
authors.lastname: Pellentz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lacoste
authors.forename: Aastha
authors.initials: A
authors.lastname: Puri
authors.forename: David C
authors.initials: DC
authors.lastname: Schultz
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Pchelintsev
authors.forename: Peter D
authors.initials: PD
authors.lastname: Adams
authors.forename: Lars E T
authors.initials: LE
authors.lastname: Jansen
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D056504:Chromatin Assembly Factor-1 / Q000378:metabolism; D004261:DNA Replication; D003851:Deoxyribonucleases / Q000378:metabolism; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C489780:CNOT8 protein, human; D018797:Cell Cycle Proteins; D056504:Chromatin Assembly Factor-1; C086057:HIRA protein, human; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; D014157:Transcription Factors; D012319:RNA Polymerase II; D003851:Deoxyribonucleases