Histone variant H2A.B-H2B dimers are spontaneously exchanged with canonical H2A-H2B in the nucleosome

Hirano, Rina; Arimura, Yasuhiro; Kujirai, Tomoya; Shibata, Mikihiro; Okuda, Aya; Morishima, Ken; Inoue, Rintaro; Sugiyama, Masaaki; Kurumizaka, Hitoshi

doi:10.1038/s42003-021-01707-z

Cited by 17 publications

(5 citation statements)

References 72 publications

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“…Deposition pattern of H2A.Bbd mostly overlaps with regions marked by H4 acetylation, indicating an active gene transcription region in the genome [ 173 , 174 ]. In addition to that, H2A.Bbd-H2B dimer is spontaneously exchanged within nucleosome with the assistance of a NAP1 histone chaperone [ 175 , 176 ]. Functionally, recent reports have shown that knockdown of H2A.Bbd resulted in an altered chromatin structure in male mouse’s post-meiotic germ cells, yet without affecting spermatogenesis [ 174 , 177 , 178 ].…”

Section: The 19 Histone H2a Variantsmentioning

confidence: 99%

Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment

Lai,

Chan

2024

IJMS

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Histones are nuclear proteins essential for packaging genomic DNA and epigenetic gene regulation. Paralogs that can substitute core histones (H2A, H2B, H3, and H4), named histone variants, are constitutively expressed in a replication-independent manner throughout the cell cycle. With specific chaperones, they can be incorporated to chromatin to modify nucleosome stability by modulating interactions with nucleosomal DNA. This allows the regulation of essential fundamental cellular processes for instance, DNA damage repair, chromosomal segregation, and transcriptional regulation. Among all the histone families, histone H2A family has the largest number of histone variants reported to date. Each H2A variant has multiple functions apart from their primary role and some, even be further specialized to perform additional tasks in distinct lineages, such as testis specific shortH2A (sH2A). In the past decades, the discoveries of genetic alterations and mutations in genes encoding H2A variants in cancer had revealed variants’ potentiality in driving carcinogenesis. In addition, there is growing evidence that H2A variants may act as novel prognostic indicators or biomarkers for both early cancer detection and therapeutic treatments. Nevertheless, no studies have ever concluded all identified variants in a single report. Here, in this review, we summarize the respective functions for all the 19 mammalian H2A variants and their roles in cancer biology whilst potentiality being used in clinical setting.

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Section: The 19 Histone H2a Variantsmentioning

confidence: 99%

Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment

Lai,

Chan

2024

IJMS

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“…Nucleosome composition in turn affects the binding dynamics of distinct histone subunits in specific regions. For instance, H2A/H2B heterodimers exchange more readily as compared to H3/H4 tetramers [18][19][20] .…”

Section: Mainmentioning

confidence: 99%

Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells

Dunjić

Jonas

Yaakov

et al. 2022

Preprint

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Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide incorporation and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by implementing a recently established, genetically encoded exchange sensor. While exchange of all measured variants scales with transcription, we describe variant-specific associations with transcription elongation and Polycomb binding. We found considerable exchange of H3.1 and H2B variants in heterochromatin and repeat elements, contrasting the stable incorporation and little exchange of H3.3 in these regions. This unexpected association between H3.3 incorporation and exchange of canonical variants is also evident in active promoters and enhancers, and further validated by reduced H3.1 dynamics following depletion of the HIRA H3.3-specific chaperone. The sensor system provides a powerful tool for studying regulation of histone dynamics toward understanding its role in shaping the epigenetic landscape in vivo.

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“…Such a histone chaperone function of the nucleosome would result in stabilized nucleosomes at the cost of freely and spontaneously exchanged histones, although spontaneous histone exchange between nucleosomes has never been reported. To support this hypothesis, spontaneous exchange of nucleosomal H2A-H2B with free H2A-H2B has been reported ( 16 , 21 , 22 ). Histone exchange among nucleosomes on a relevant timescale would imply that histone modifications and variants can diffuse and redistribute themselves spontaneously in chromatin after serving their purpose.…”

mentioning

confidence: 93%