Placing the HIRA Histone Chaperone Complex in the Chromatin Landscape
Open accessAbstract
The HIRA chaperone complex, comprised of HIRA, UBN1, and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand HIRA's function and mechanism, we integrated HIRA, UBN1, ASF1a, and histone H3.3 chromatin immunoprecipitation sequencing and gene expression analyses. Most HIRA-binding sites colocalize with UBN1, ASF1a, and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and coregulator composition at different classes of HIRA-bound regulatory sites. Underscoring this, we report physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodeling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites.
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HIRA mediates the replacement of canonical H3 with the H3.3 variant at promoters.
“HIRA mediates the replacement of canonical H3 with the H3.3 variant at promoters52, and continuous H3.3 exchange has been proposed to keep these sites transiently exposed, allowing transcription factors to access their binding sites53.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [52]
In human, histone chaperones HIRA and ASF1a localise at active promoters where BRG1, a human SWI/SNF complex subunit, also localises.
“In human, histone chaperones HIRA and ASF1a localise at active promoters where BRG1, a human SWI/SNF complex subunit, also localises52.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [52]
At promoters, human HIRA and ASF1a essentially localise to nucleosome-free TSSs.
“Interestingly, at promoters, human HIRA and ASF1a essentially localise to nucleosome-free TSSs52, reminiscent of our findings that yeast Rtt106 is enriched at wider nucleosome-free regions upstream of TSSs (Fig. 2g).”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [52]
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References 45 · Cited by 143
- Authors
- Pchelintsev, N. A., McBryan, T., Rai, T. S., van Tuyn, J., Ray-Gallet, D., Almouzni, G., & Adams, P. D.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Adams, Peter D.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 3
- Issue
- 4
- Pages
- 1012-1019
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC3974909
- OpenAlex
- W2029151607
- Cited by
- 143
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 15 · 2019: 8 · 2018: 16 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 10 · 2013: 7
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Cancer Research UK (C10652/A10250)
- Ligue Contre le Cancer
- National Institute on Aging (P01AG031862, AG031862-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- CABIN1, ASF1A, ChIP-seq, promoter binding, enhancer binding, transcription factor interaction, chromatin insulators, chromatin remodeling complexes, gene expression regulation
- MeSH terms
- Binding Sites, Chromatin, HeLa Cells, Histones, Humans, Nuclear Proteins, Promoter Regions, Genetic, Transcription Factors, Cluster Analysis, Cell Cycle Proteins, Molecular Chaperones, RNA Interference, RNA, Small Interfering, Chromatin Immunoprecipitation, Genetic Loci, Histone Chaperones
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