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Updated: Jul 29, 2025
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Interplay between PML NBs and HIRA for H3.3 dynamics following type I interferon stimulus
Constance Kleijwegt1, Florent Bressac1, Coline Seurre1
1University of Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U 1315, LabEx DEVweCAN, Institut NeuroMyoGène (INMG), Pathophysiology and Genetics of the Neuron and Muscle (PGNM) laboratory, team Chromatin Dynamics, Nuclear Domains, Virus, Lyon, France.
Promyelocytic leukemia nuclear bodies (PML NBs) act as nuclear depots, regulating HIRA distribution via SUMO-SIM interactions. They also control interferon-stimulated gene transcription and H3.3 deposition during inflammatory responses.
Area of Science:
- Cell Biology
- Molecular Biology
- Genomics
Background:
- Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic, membrane-less nuclear structures linked to chromatin.
- The H3.3 histone chaperone complex HIRA is known to accumulate in PML NBs under specific cellular conditions like senescence or viral infection.
- The precise mechanisms governing HIRA's recruitment to PML NBs and its functional implications for histone dynamics were not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying HIRA recruitment to PML NBs.
- To investigate the role of PML NBs in regulating HIRA distribution and histone dynamics.
- To understand the function of PML NBs in interferon-stimulated gene (ISG) transcription and H3.3 deposition.
Main Methods:
- Utilized specific biochemical and imaging approaches to study HIRA-PML NB interactions.
- Investigated the role of SUMO-SIM interactions in HIRA recruitment.
- Analyzed the impact of PML, SP100, and DAXX/H3.3 levels on HIRA distribution.
- Examined gene transcription and histone deposition dynamics upon IFN-I stimulation.
Main Results:
- Identified intermolecular SUMO-SIM interactions as a key mechanism for HIRA recruitment into PML NBs.
- Demonstrated that PML NBs function as nuclear depots, controlling HIRA distribution dependent on SP100 and DAXX/H3.3.
- Showed that PML is essential for ISG transcription and PML NBs associate with ISG loci upon IFN-I stimulation.
- Found that HIRA and PML are required for sustained H3.3 deposition at ISG transcriptional end sites, although HIRA's presence in PML NBs is not essential for this deposition.
Conclusions:
- PML NBs play a dual role: buffering HIRA nuclear distribution and acting as chromosomal hubs for ISG regulation.
- PML NBs modulate HIRA nuclear distribution through SUMO-SIM interactions.
- PML NBs are critical for inflammatory responses, influencing ISG transcription and HIRA-mediated H3.3 deposition.
