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| Status |
Public on May 30, 2023 |
| Title |
Interplay between PML NBs and HIRA for H3.3 deposition on transcriptionally active interferon-stimulated genes |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Promyelocytic Leukemia Nuclear Bodies (PML NBs) are nuclear membrane-less organelles physically associated with chromatin underscoring their crucial role in genome function. The H3.3 histone chaperone complex HIRA accumulates in PML NBs upon senescence, viral infection or IFN-I treatment in primary cells. Yet, the molecular mechanisms of this partitioning and its function in regulating histone dynamics have remained elusive. Here, by using specific siRNAs and protein Affimers, we identify intermolecular SUMO-SIM interactions as an essential mechanism for HIRA recruitment in PML NBs. In addition, we demonstrate that HIRA localization in the nuclear bodies is intimately linked to the presence of a soluble pool of H3.3-H4 dimers inside PML NBs, that is not found in cancer cells. Transcription inhibition prevents HIRA accumulation in PML NBs underscoring the importance of transcriptional activity to drive HIRA through PML NBs. Finally, in the context of inflammatory responses, HIRA and PML are necessary for the prolonged H3.3 deposition at the transcriptional end sites of interferon-stimulated genes (ISGs), well beyond the peak of transcription. We thus propose that HIRA partitioning in PML NBs is essential to regulate H3.3 deposition on transcriptionally active regions.
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| |
|
| Overall design |
H3.3 ChIP-seq on human primary BJ cells treated with siLuc, sILuc+IFN, siHIRA+IFN or siPML+IFN
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| |
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| Contributor(s) |
Constance K, Armelle C, Patrick L, Thomas S |
| Citation missing |
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| |
| Submission date |
Nov 01, 2021 |
| Last update date |
May 31, 2023 |
| Contact name |
Thomas Simonet |
| E-mail(s) |
[email protected]
|
| Phone |
+33 662035723
|
| Organization name |
Université de Lyon
|
| Lab |
Institut NeuroMyoGene
|
| Street address |
Faculté de Médecine Lyon Est, 8 Avenue Rockefeller
|
| City |
Lyon |
| ZIP/Postal code |
69008 |
| Country |
France |
| |
|
| Platforms (1) |
|
| Samples (8)
|
| GSM5663898 |
Input DNA – siRNA anti-Luc – No treatment |
| GSM5663899 |
ChIP anti-H3.3 – siRNA anti-Luc – No treatment |
| GSM5663900 |
Input DNA – siRNA anti-Luc – IFN treated |
| GSM5663901 |
ChIP anti-H3.3 – siRNA anti-Luc – IFN treated |
| GSM5663902 |
Input DNA – siRNA anti-HIRA – IFN treated |
| GSM5663903 |
ChIP anti-H3.3 – siRNA anti-HIRA – IFN treated |
| GSM5663904 |
Input DNA – siRNA anti-PML – IFN treated |
| GSM5663905 |
ChIP anti-H3.3 – siRNA anti-PML – IFN treated |
|
| Relations |
| BioProject |
PRJNA776846 |
| SRA |
SRP344040 |
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