Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Sundaramoorthy, Ramasubramanian; Hughes, Amanda L.; Mkami, Hassane El; Norman, D.; Ferreira, Helder; Owen-Hughes, Tom

doi:10.7554/elife.35720

Cited by 76 publications

(111 citation statements)

References 110 publications

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“…The ATPase motor is in a closed, post-translocated state with AMP-PNP bound in the active site. A similar state was observed for Chd1 when bound to ADP·BeF 3 (Farnung et al, 2017;Sundaramoorthy et al, 2018Sundaramoorthy et al, , 2017. The double chromodomain is located at SHL +1 and contacts the nucleosomal DNA phosphate backbone via electrostatic interactions, in a fashion similar to that observed for S. cerevisiae Chd1 ( Fig.…”

Section: Resultssupporting

confidence: 77%

“…1). Binding at this location has also been observed for the chromatin remodellers Chd1 (Farnung et al, 2017;Sundaramoorthy et al, 2018), Snf2 (Liu et al, 2017), and Swr1 (Willhoft et al, 2018). The ATPase motor is in a closed, post-translocated state with AMP-PNP bound in the active site.…”

Section: Resultsmentioning

confidence: 71%

“…This contact is critical for chromatin remodelling. Deletion of the homologous region in Chd1 leads to abolishment of chromatin remodelling activity (Sundaramoorthy et al, 2018). However, it remains unclear if these contacts are required for proper substrate recognition and positioning or whether they are also necessary to generate the force required for DNA translocation.…”

Section: Resultsmentioning

confidence: 99%

“…Gly1003 in ATPase lobe2 is located in a loop near H3 alpha helix 1. Deletion of this loop in Chd1 results in a loss of chromatin remodelling activity (Sundaramoorthy et al, 2018). Residue Arg1068 forms a hydrogen bond network with the side chain of Thr1137 and the main chain carbonyl groups of Phe1112 and Gln1119.…”

Section: Cancer-related Chd4 Mutationsmentioning

confidence: 99%

“…Recent structures of the yeast remodeller Chd1 in complex with a nucleosome uncovered the architecture of one subfamily of CHD remodellers (subfamily I) and its interactions with the nucleosome (Farnung et al, 2017;Sundaramoorthy et al, 2018). A unique feature of these structures is that Chd1 binding induces unwrapping of terminal DNA from the histone octamer surface at superhelical location (SHL) -6 and -7 (Farnung et al, 2017;Sundaramoorthy et al, 2018). However, the resolution of these studies was limited, such that atomic details were not resolved.…”

Section: Introductionmentioning

confidence: 99%

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Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Farnung

Ochmann

Cramer

2019

Preprint

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The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our results also rationalize the effect of CHD4 mutations that are associated with cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Cancer-related Chd4 Mutationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Farnung

Ochmann

Cramer

2019

Preprint

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Structural Basis of Nucleosome Recognition and Modulation

Sundaram

Vasudevan

2020

BioEssays

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Chromatin structure and dynamics regulate key cellular processes such as DNA replication, transcription, repair, remodeling, and gene expression, wherein different protein factors interact with the nucleosomes. In these events, DNA and RNA polymerases, chromatin remodeling enzymes and transcription factors interact with nucleosomes, either in a DNA‐sequence‐specific manner and/or by recognizing different structural features on the nucleosome. The molecular details of the recognition of a nucleosome by different viral proteins, remodeling enzymes, histone post‐translational modifiers, and RNA polymerase II, have been explored in the recent past. The present review puts forth critical insights into the basic mechanisms of nucleosome recognition by the various protein factors and the role of distinct surface epitopes on a nucleosome. These determinants of the underlying specificity include features such as the acidic patch, arginine anchor, histone post‐translational modifications, core DNA, DNA lesions, and linker DNA.

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Molecular basis for chromatin assembly and modification by multiprotein complexes

et al. 2018

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Epigenetic regulation of the chromatin landscape is often orchestrated through modulation of nucleosomes. Nucleosomes are composed of two copies each of the four core histones, H2A, H2B, H3, and H4, wrapped in ~150 bp of DNA. We focus this review on recent structural studies that further elucidate the mechanisms used by macromolecular complexes to mediate histone modification and nucleosome assembly. Nucleosome assembly, spacing, and variant histone incorporation are coordinated by chromatin remodeler and histone chaperone complexes. Several recent structural studies highlight how disparate families of histone chaperones and chromatin remodelers share similar features that underlie how they interact with their respective histone or nucleosome substrates. Posttranslational modification of histone residues is mediated by enzymatic subunits within large complexes. Until recently, relatively little was known about how association with auxiliary subunits serves to modulate the activity and specificity of the enzymatic subunit. Analysis of several recent structures highlights the different modes that auxiliary subunits use to influence enzymatic activity or direct specificity toward individual histone residues.

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Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Cited by 76 publications

References 110 publications

Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Structural Basis of Nucleosome Recognition and Modulation

Molecular basis for chromatin assembly and modification by multiprotein complexes

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