Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility

Li, Shuxiang; Wei, Tiejun; Panchenko, Anna R.

doi:10.1038/s41467-023-36465-5

Cited by 30 publications

(26 citation statements)

References 93 publications

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“…Transcription factor binding motifs close to the nucleosome entry-exit sites may have increased exposure but would be error- prone to capture using MNase-seq data as a nucleotide bias exists around the ends of nucleosomal DNA reads produced by the MNase-seq experiments. Moreover, as we showed recently the degree of spontaneous DNA unwrapping from nucleosomes depends on the incorporation of histone variants, like H2A.Z 74 , which is, in turn, might be needed for pioneer transcription factor recruitment to promote embryonic stem cell differentiation 75 . The third important group of limitations pertains to the nucleosome positioning in a genome, as binding dissociation constants for PTFs depend on where nucleosomes are located.…”

Section: Discussionmentioning

confidence: 87%

Detection of new pioneer transcription factors as cell-type specific nucleosome binders

Peng

Song

Teif

et al. 2023

Preprint

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Wrapping of DNA into nucleosomes restricts DNA accessibility and the recognition of binding motifs by transcription factors. A certain class of transcription factors, so-called pioneer transcription factors, can specifically recognize their binding sites on nucleosomal DNA, initiate local chromatin opening and facilitate the binding of co-factors in a cell-type-specific manner. For the vast majority of human pioneer transcription factors, the locations of their binding sites, mechanisms of binding and regulation remain unknown. We have developed a computational method to predict the cell-type-specific ability of transcription factors to bind nucleosomes by integrating ChIP-seq, MNaseq-seq and DNase-seq data with the details of nucleosome structure. We have achieved classification accuracy with AUC=0.94 in discriminating pioneer factors from canonical transcription factors and predicted 32 potential pioneer transcription factors as nucleosome binders in embryonic cell differentiation. Lastly, we systemically analyzed the interaction modes between various pioneer factors and detected several clusters of distinctive binding sites on nucleosomal DNA.

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Section: Discussionmentioning

confidence: 87%

Detection of new pioneer transcription factors as cell-type specific nucleosome binders

Peng

Song

Teif

et al. 2023

Preprint

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“…The incorporation of histone variants H2A.Z and/or H3.3 into nucleosomes can generate fragile variant nucleosomes which can partially unwrap (Jin et al , 2009; Li et al , 2023; Wen et al , 2020). They are enriched at the +1 and -1 nucleosome positions downstream and upstream of active TSSs and as flanking arrays at CTCF binding sites (Jin et al , 2009; Wen et al , 2020).…”

Section: Resultsmentioning

confidence: 99%

“…The size distributions of H3.3-associated fragments are skewed towards larger values that H2A.Z-associated fragments. H2A.Z has been described as a major factor associated to subnucleosomes (Li et al, 2023). We analysed nucleosome positioning in mESCs where H2A.Z had been knocked down by siRNA ( Taken together, these results highlight that the implication of histone variants H2A.Z and H3.3 in small-size particles is not identical between the 3 NDR types and the bulk.…”

Section: Subnucleosomes At Niebs Borders Are Independent Of Histone V...mentioning

confidence: 90%

“…Unwrapping events can result in partial destabilization, forming subnucleosomal particles like hexasomes, or complete eviction of the octamer. Histone variants and modifications, as well as linker histones, can influence nucleosome dynamics and breathing (Konrad et al , 2022; Li et al , 2023). The control mechanisms for wrapping/unwrapping dynamics, such as the role of DNA sequence or epigenetic marks, are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Decoding Nucleosome-Depleted Regions: Insights from Epigenetic Marks, Nucleosome Size, and Thermodynamic Modelling

Tartour,

Barbier,

Hungyo

et al. 2023

Preprint

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Elucidating the global and local rules that govern genome-wide nucleosome organisation and chromatin architecture remains a critical challenge. Thermodynamic modelling based on DNA elastic properties predicts the presence of sequence-encoded nucleosome-inhibiting energy barriers (NIEBs) along vertebrate genomes. They delineate in vivo nucleosome-depleted regions (NDRs) flanked by 2-3 well positioned nucleosomes. Here, we compared mouse NIEBs to NDRs observed at CTCF binding sites and active TSSs to reveal specific chromatin organizations. We uncover in MNase-seq chromatin profiles the presence of particles of subnucleosomal length specifically positioned at the border of NIEBs with an enrichment of H3.3 and its modification H3.3 S31Ph, whereas the positioning of nucleosomes bearing H3K27ac appears insensitive to NIEBs. Surprisingly, post-translational modifications affect the size distribution of nucleosomes as seen by MNase digestion and so likely their breathing capability. We implemented an extension of our thermodynamic model allowing for variable particle size and suggest that subnucleomes at NIEB borders would result from the recruitment of chromatin remodellers at NIEBs. Our findings provide new insights into the mechanisms by which the DNA sequence and epigenetic marks shape the nucleosome positioning and breathing.

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“…A more open, nucleosomal structure, experimentally induced in the canonical nucleosomes by salt, could accommodate the C-terminal tail of a juxtaposed H2A.Z nucleosome. The tail of the histone variant is likely to protrude out of the nucleosome so as to be able to reach a binding site in a neighboring chromatin fiber 61, 62 . The relaxed state of plasmid DNA in the reconstituted nucleosomal arrays of our hydroxyapatite experiments (see Materials and Methods; Fig.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Modulation via the C-Terminal Tail of H2A.Z

Imre

Nánási

Bosire

et al. 2021

Preprint

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Nucleosome stability, a crucial determinant of gene regulation, was measured in a robust in situ assay to assess the molecular determinants of the stability of H2A.Z-containig nucleosomes. Surprisingly, a large fraction of H2A.Z detected by three different antibodies was released from the nucleosomes by salt together with H3, and was associated with H3K9me3 but not with H3K27me3 marked nucleosomes. This unusual behavior relied on the presence of the unstructured C-terminal chain of the histone variant, rather than on isoform specificity, posttranslational modifications or binding of the reader protein PWWPA2, as determined using cell lines expressing only particular forms of the variant. In the absence of this tail, or upon addition of an excess of the tail peptide to the nuclei of control cells, the canonical H2A-like stability features were readily restored and most of the H2A.Z-containing nucleosomes left the periphery and ended up in scattered foci in the nuclei. Concomitantly, the H3K9me3-marked constitutive heterochromatin was also dispersed, what was accompanied by increased overall nuclease sensitivity and significantly enhanced binding of intercalating dyes to the DNA. The DT40 cells expressing the tailless H2A.Z showed marked differences in their gene expression pattern and were distinguished by compromised DNA damage response. Thus, interactions involving a short H2A.Z peptide chain simultaneously determine the stability and accessibility features of chromatin involving the nucleosomes containing this histone variant and the localization of these large chromatin regions in the nucleus. Our data suggest that H2A.Z can function in both heterochromatic and in euchromatic scenarios depending on the molecular interactions involving its C-terminal unstructured tail, shedding light on the enigmatic double-faced character of this histone variant.

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Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility

Cited by 30 publications

References 93 publications

Detection of new pioneer transcription factors as cell-type specific nucleosome binders

Detection of new pioneer transcription factors as cell-type specific nucleosome binders

Decoding Nucleosome-Depleted Regions: Insights from Epigenetic Marks, Nucleosome Size, and Thermodynamic Modelling

Epigenetic Modulation via the C-Terminal Tail of H2A.Z

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