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Factors influencing in vivo deposition of histone variants H3.1 and H3.3


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. Remarkably, the HIRA complex shows unique DNA binding properties and depleting HIRA increases DNA sensitivity to nucleases. We propose that protective 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. Examination of genome-wide localization of two histone H3 variants.

ORGANISM(S): Homo sapiens

SUBMITTER: Genevieve Almouzni 

PROVIDER: E-GEOD-31794 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Ray-Gallet Dominique D   Woolfe Adam A   Vassias Isabelle I   Pellentz Céline C   Lacoste Nicolas N   Puri Aastha A   Schultz David C DC   Pchelintsev Nikolay A NA   Adams Peter D PD   Jansen Lars E T LE   Almouzni Geneviève G  

Molecular cell 20111201 6


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  ...[more]

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