The H2A.Z-nucleosome code in mammals: emerging functions

Colino‐Sanguino, Yolanda; Clark, Susan J.; Valdés-Mora, Fátima

doi:10.1016/j.tig.2021.10.003

Cited by 47 publications

(31 citation statements)

References 151 publications

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“…Essential in mammalian cells, H2A.Z has crucial roles in the regulation of gene expression, DNA repair, chromosome segregation, and maintenance of heterochromatin-euchromatin boundaries [5,7,8]. As a result, H2A.Z has been associated with a diverse set of biological functions in mammals [9] including memory [10][11][12][13][14], the epithelial-to-mesenchymal transition [15,16], embryonic development [17], and cell proliferation in cancer [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

What makes a histone variant a variant: Changing H2A to become H2A.Z

et al. 2021

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Chromatin structure and underlying DNA accessibility is modulated by the incorporation of histone variants. H2A.Z, a variant of the H2A core histone family, plays a distinct and essential role in a diverse set of biological functions including gene regulation and maintenance of heterochromatin-euchromatin boundaries. Although it is currently unclear how the replacement of H2A with H2A.Z can regulate gene expression, the variance in their amino acid sequence likely contributes to their functional differences. To tease apart regions of H2A.Z that confer its unique identity, a set of plasmids expressing H2A-H2A.Z hybrids from the native H2A.Z promoter were examined for their ability to recapitulate H2A.Z function. First, we found that the H2A.Z M6 region was necessary and sufficient for interaction with the SWR1-C chromatin remodeler. Remarkably, the combination of only 9 amino acid changes, the H2A.Z M6 region, K79 and L81 (two amino acids in the α2-helix), were sufficient to fully rescue growth phenotypes of the htz1Δ mutant. Furthermore, combining three unique H2A.Z regions (K79 and L81, M6, C-terminal tail) was sufficient for expression of H2A.Z-dependent heterochromatin-proximal genes and GAL1 derepression. Surprisingly, hybrid constructs that restored the transcription of H2A.Z-dependent genes, did not fully recapitulate patterns of H2A.Z-specific enrichment at the tested loci. This suggested that H2A.Z function in transcription regulation may be at least partially independent of its specific localization in chromatin. Together, this work has identified three regions that can confer specific H2A.Z-identity to replicative H2A, furthering our understanding of what makes a histone variant a variant.

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Section: Introductionmentioning

confidence: 99%

What makes a histone variant a variant: Changing H2A to become H2A.Z

et al. 2021

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“…In primates, the H2AFV RNA can be alternatively spliced giving rise to an additional H2A.Z.2.2 protein with a shortened C-terminus that destabilizes nucleosomes 4, 5 . Importantly, H2A.Z has been demonstrated to be essential for embryogenesis and is involved in neurodevelopmental processes 2, 6–8 . However, the underlying molecular mechanism(s) remains ill-defined, although H2A.Z has been implicated in many DNA-based processes including transcriptional regulation, cell cycle control and DNA repair 8–13 .…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, H2A.Z has been demonstrated to be essential for embryogenesis and is involved in neurodevelopmental processes 2, 6–8 . However, the underlying molecular mechanism(s) remains ill-defined, although H2A.Z has been implicated in many DNA-based processes including transcriptional regulation, cell cycle control and DNA repair 8–13 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…However, the underlying molecular mechanism(s) remains ill-defined, although H2A.Z has been implicated in many DNA-based processes including transcriptional regulation, cell cycle control and DNA repair [8][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

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The H2A.Z.1/PWWP2A/NuRD-associated protein HMG20A controls early head and heart developmental transcription programs

Herchenröther

Gossen

Friedrich

et al. 2022

Preprint

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Abstract/SummarySpecialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes including NuRD, and show that it localizes to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis. Our data indicate that craniofacial malformations are caused by defects in neural crest cell (NCC) migration and cartilage formation. These developmental defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CMs). Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial- mesenchymal transition (EMT) and cardiac differentiation, thereby providing insights into the regulatory circuits controlled by HMG20A. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of the intricate developmental transcription programs that guide NCC and cardiomyocyte differentiation.

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Cloning and characterization of the histone variant gene H2A.Z in Bombyx mori

Mei,

Xu,

Huang

et al. 2024

Arch Insect Biochem Physiol

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H2A.Z, the most evolutionarily conserved variant of histone H2A, plays a pivotal role in chromatin remodeling and contributes significantly to gene transcription and genome stability. However, the role of H2A.Z in the silkworm (Bombyx mori) remains unclear. In this study, we cloned the BmH2A.Z from B. mori. The open reading frame of BmH2A.Z is 390 bp, encoding 129 amino acids, with a confirmed molecular weight of 13.4 kDa through prokaryotic expression analysis. Sequence analysis revealed that BmH2A.Z has a conserved H2A.Z domain and is closely related to the systemic evolution of other known H2A.Zs. The expression profile of BmH2A.Z at various developmental stages of the B. mori exhibited the highest expression level in the 1st instar, followed by the grain stage and the 2nd instar, and the lowest expression level in the moth. The highest transcript level of BmH2A.Z was observed in the head, with relatively lower levels detected in the blood than in the other tissues under consideration. In addition, the upregulation of BmH2A.Z resulted in the amplified expression of B. mori nucleopolyhedrovirus (BmNPV) genes, thus facilitating the proliferation of BmNPV. This study establishes a foundation for investigating the role of BmH2A.Z in B. mori and its participation in virus‐host interactions.

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The H2A.Z-nucleosome code in mammals: emerging functions

Cited by 47 publications

References 151 publications

What makes a histone variant a variant: Changing H2A to become H2A.Z

What makes a histone variant a variant: Changing H2A to become H2A.Z

The H2A.Z.1/PWWP2A/NuRD-associated protein HMG20A controls early head and heart developmental transcription programs

Cloning and characterization of the histone variant gene H2A.Z in Bombyx mori

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