HIRA defines early replication initiation zones independently of their genome compartment

Tina Karagyozova, Alberto Gatto, Audrey Forest, Jean-Pierre Quivy, Rocío Nunez-Vazquez, Marc A. Martí-Renom, Leonid A. Mirny and Geneviève Almouzni ()
Additional contact information
Tina Karagyozova: Equipe Labellisée Ligue contre le Cancer
Alberto Gatto: Equipe Labellisée Ligue contre le Cancer
Audrey Forest: Equipe Labellisée Ligue contre le Cancer
Jean-Pierre Quivy: Equipe Labellisée Ligue contre le Cancer
Rocío Nunez-Vazquez: Equipe Labellisée Ligue contre le Cancer
Marc A. Martí-Renom: Centre Nacional d’Anàlisi Genòmica (CNAG)
Leonid A. Mirny: Massachusetts Institute of Technology
Geneviève Almouzni: Equipe Labellisée Ligue contre le Cancer

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Chromatin states and 3D architecture have been used as proxy to identify replication initiation zones (IZs) in mammalian cells, yet their functional interconnections remain a puzzle. Here, to dissect these relationships, we focus on the histone H3.3 chaperone HIRA recently implicated in early initiation zone (IZ) definition. We monitor 3D organisation, chromatin accessibility and histone post-translational modifications (PTMs) in wild-type and HIRA knock-out cells in parallel with early replication initiation. In the absence of HIRA, compartment A loses H3.3 enrichment and gains accessibility without changes in associated histone post-translational modifications (PTMs). Furthermore, impaired early firing at HIRA-dependent IZs does not correspond to changes in chromatin accessibility or patterns of histone H3 PTMs. Additionally, a small subset of early IZs initially in compartment A switch to B and lose early initiation in the absence of HIRA. Critically, HIRA complementation restores these early IZ, and H3.3 variant enrichment, without substantial compartment reversal. Thus, while HIRA contributes to compartment A features, its role in regulating early replication initiation can be uncoupled from accessibility, histone marks and compartment organisation.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65130-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65130-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65130-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().