Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Dombrowski, Marco; Engeholm, Maik; Dienemann, Christian; Dodonova, S.O.; Cramer, Patrick

doi:10.1038/s41594-022-00768-w

Cited by 50 publications

(40 citation statements)

References 70 publications

(141 reference statements)

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“…4e, II, red-dashed line). This experiment suggests H1 reduced the freedom range of two DNA linkers as reported 60 , while increasing the connectivity among the NCPs but not significantly reducing the overall diameter.…”

Section: Effect Of H1 On the 3d Structural Dynamics Of Tetranucleosomessupporting

confidence: 53%

Conformational Change of Nucleosome Arrays prior to Phase Separation

Zhang

Celis

Liu

et al. 2023

Preprint

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Chromatin phase transition serves as a regulatory mechanism for eukaryotic transcription. Understanding this process requires the characterization of the nucleosome array structure in response to external stimuli prior to phase separation. However, the intrinsic flexibility and heterogeneity hinders the arrays’ structure determination. Here we exploit advances in cryogenic electron tomography (cryo-ET) to determine the three-dimensional (3D) structure of each individual particle of mono-, di-, tri-, and tetranucleosome arrays. Statistical analysis reveals the ionic strength changes the angle between the DNA linker and nucleosome core particle (NCP), which regulate the overall morphology of nucleosome arrays. The finding that one-third of the arrays in the presence of H1 contain an NCP invaded by foreign DNA suggests an alternative function of H1 in constructing nucleosomal networks. The new insights into the nucleosome conformational changes prior to the intermolecular interaction stage extends our understanding of chromatin phase separation regulation.

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Section: Effect Of H1 On the 3d Structural Dynamics Of Tetranucleosomessupporting

confidence: 53%

Conformational Change of Nucleosome Arrays prior to Phase Separation

Zhang

Celis

Liu

et al. 2023

Preprint

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“…The BAP1/ASXL1 DNA clamp on the dyad, H2A docking domain in the canonical nucleosome conformation, and histone H1.4 all occupy almost the same location (43,44).…”

Section: Discussionmentioning

confidence: 99%

Structural basis of histone H2A lysine 119 deubiquitination by Polycomb Repressive Deubiquitinase BAP1/ASXL1

Thomas

Valencia-Sánchez

Tamburri

et al. 2023

Preprint

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The maintenance of gene expression patterns during metazoan development is achieved by the actions of Polycomb group (PcG) complexes. An essential modification marking silenced genes is monoubiquitination of histone H2A lysine 119 (H2AK119Ub) deposited by the E3 ubiquitin ligase activity of the non-canonical Polycomb Repressive Complex 1. The Polycomb Repressive Deubiquitinase (PR-DUB) complex cleaves monoubiquitin from histone H2A lysine 119 (H2AK119Ub) to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. BAP1 and ASXL1, subunits that form active PR-DUB, are among the most frequently mutated epigenetic factors in human cancers, underscoring their biological importance. How PR-DUB achieves specificity for H2AK119Ub to regulate Polycomb silencing is unknown, and the mechanisms of most of the mutations in BAP1 and ASXL1 found in cancer have not been established. Here we determine a cryo-EM structure of human BAP1 bound to the ASXL1 DEUBAD domain in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for remodeling the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing new insight into understanding cancer etiology.

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“…S4 B). This cooperative nucleosome stacking clearly presents the major energetic barrier for chromatin unfolding and is strongly dependent on the linker DNA length (Brouwer et al, 2021; Dombrowski et al, 2022). The nucleosome surfaces including the unique acidic patch that become closed by the nucleosome stacking are the sites of interaction with multiple chromatin regulatory and architectural factors (Skrajna et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Cryo-electron tomography reveals the multiplex anatomy of condensed native chromatin and its unfolding by histone citrullination

Jentink

Purnell

Kable

et al. 2022

Preprint

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Nucleosome chains fold and self-associate to form higher order structures whose internal organization is unknown. Here, cryo-electron tomography (cryo-ET) of native human chromatin reveals novel folding motifs such as 1) non-uniform nucleosome stacking, 2) intermittent parallel and perpendicular orientations of adjacent nucleosome planes, and 3) an inverse zigzag nucleosome chain path, which deviates from the direct zigzag topology seen in reconstituted nucleosomal arrays. By examining these self-associated structures, we observed prominent nucleosome stacking in-cis and anti-parallel nucleosome interactions in-trans, which are consistent with partial nucleosome interdigitation. Histone citrullination strongly inhibits nucleosome stacking and self-association with a modest effect on chromatin folding, while the reconstituted arrays showed a zigzag topology which undergoes a dramatic unfolding induced by histone citrullination. This study sheds light on the internal structure of compact chromatin nanoparticles and suggests a novel mechanism for how epigenetic changes in chromatin are retained across both open and condensed forms of chromatin.

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Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Cited by 50 publications

References 70 publications

Conformational Change of Nucleosome Arrays prior to Phase Separation

Conformational Change of Nucleosome Arrays prior to Phase Separation

Structural basis of histone H2A lysine 119 deubiquitination by Polycomb Repressive Deubiquitinase BAP1/ASXL1

Cryo-electron tomography reveals the multiplex anatomy of condensed native chromatin and its unfolding by histone citrullination

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