Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

2.3 A structure of the ATP-dependent chromatin remodeler Chd1 bound to the nucleosome in a nucleotide-free state

ABSTRACT:

SUBMITTER: Jean-Paul Armache

PROVIDER: EMPIAR-10876 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Nucleosome recognition and DNA distortion by the Chd1 remodeler in a nucleotide-free state.

Nodelman Ilana M IM Das Sayan S Faustino Anneliese M AM Fried Stephen D SD Bowman Gregory D GD Armache Jean-Paul JP

Nature structural & molecular biology 20220216 2

Chromatin remodelers are ATP-dependent enzymes that reorganize nucleosomes within all eukaryotic genomes. Here we report a complex of the Chd1 remodeler bound to a nucleosome in a nucleotide-free state, determined by cryo-EM to 2.3 Å resolution. The remodeler stimulates the nucleosome to absorb an additional nucleotide on each strand at two different locations: on the tracking strand within the ATPase binding site and on the guide strand one helical turn from the ATPase motor. Remarkably, the ad ...[more]

PMID: 35173352

Similar Datasets

Bi-directional nucleosome sliding by the Chd1 chromatin remodeler integrates intrinsic sequence-dependent and ATP-dependent nucleosome positioning.

Project description:Chromatin remodelers use a helicase-type ATPase motor to shift DNA around the histone core. Although not directly reading out the DNA sequence, some chromatin remodelers exhibit a sequence-dependent bias in nucleosome positioning, which presumably reflects properties of the DNA duplex. Here, we show how nucleosome positioning by the Chd1 remodeler is influenced by local DNA perturbations throughout the nucleosome footprint. Using site-specific DNA cleavage coupled with next-generation sequencing, we show that nucleosomes shifted by Chd1 can preferentially localize DNA perturbations - poly(dA:dT) tracts, DNA mismatches, and single-nucleotide insertions - about a helical turn outside the Chd1 motor domain binding site, super helix location 2 (SHL2). This phenomenon occurs with both the Widom 601 positioning sequence and the natural +1 nucleosome sequence from the Saccharomyces cerevisiae SWH1 gene. Our modeling indicates that localization of DNA perturbations about a helical turn outward from SHL2 results from back-and-forth sliding due to remodeler action on both sides of the nucleosome. Our results also show that barrier effects from DNA perturbations can be extended by the strong phasing of nucleosome positioning sequences.

| S-EPMC10602870 | biostudies-literature

The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution.

Project description:Isw1 and Chd1 are ATP-dependent nucleosome-spacing enzymes required to establish regular arrays of phased nucleosomes near transcription start sites of yeast genes. Cells lacking both Isw1 and Chd1 have extremely disrupted chromatin, with weak phasing, irregular spacing and a propensity to form close-packed dinucleosomes. The Isw1 ATPase subunit occurs in two different remodeling complexes: ISW1a (composed of Isw1 and Ioc3) and ISW1b (composed of Isw1, Ioc2 and Ioc4). The Ioc4 subunit of ISW1b binds preferentially to the H3-K36me3 mark. Here we show that ISW1b is primarily responsible for setting nucleosome spacing and resolving close-packed dinucleosomes, whereas ISW1a plays only a minor role. ISW1b and Chd1 make additive contributions to dinucleosome resolution, such that neither enzyme is capable of resolving all dinucleosomes on its own. Loss of the Set2 H3-K36 methyltransferase partly phenocopies loss of Ioc4, resulting in increased dinucleosome levels with only a weak effect on nucleosome spacing, suggesting that Set2-mediated H3-K36 trimethylation contributes to ISW1b-mediated dinucleosome separation. The H4 tail domain is required for normal nucleosome spacing but not for dinucleosome resolution. We conclude that the nucleosome spacing and dinucleosome resolving activities of ISW1b and Chd1 are critical for normal global chromatin organisation.

| S-EPMC7892562 | biostudies-literature

Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.

Project description:The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks.

| S-EPMC8463071 | biostudies-literature

dCHD3, a novel ATP-dependent chromatin remodeler associated with sites of active transcription.

Project description:ATP-dependent chromatin remodelers of the CHD family play important roles during differentiation and development. Three CHD proteins, dMi-2, dChd1, and Kismet, have been described for Drosophila melanogaster. Here, we study dCHD3, a novel member of the CHD family. dCHD3 is related in sequence to dMi-2 but lacks several domains implicated in dMi-2 function. We demonstrate that dCHD3 is a nuclear protein and that expression is tightly regulated during fly development. Recombinant dCHD3 remodels mono- and polynucleosomes in an ATP-dependent manner in vitro. Its chromodomains are critical for nucleosome binding and remodeling. Unlike dMi-2, dCHD3 exists as a monomer. Nevertheless, both proteins colocalize with RNA polymerase II to actively transcribed regions on polytene chromosomes, suggesting that both remodelers participate in the process of transcription.

| S-EPMC2293103 | biostudies-literature

Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations.

Project description:Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling 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 remodeling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.

| S-EPMC7338049 | biostudies-literature

Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler.

Project description:Posttranslational modifications play a key role in recruiting chromatin remodeling and modifying enzymes to specific regions of chromosomes to modulate chromatin structure. Alc1 (amplified in liver cancer 1), a member of the SNF2 ATPase superfamily with a carboxy-terminal macrodomain, is encoded by an oncogene implicated in the pathogenesis of hepatocellular carcinoma. Here we show that Alc1 interacts transiently with chromatin-associated proteins, including histones and the poly(ADP-ribose) polymerase Parp1. Alc1 ATPase and chromatin remodeling activities are strongly activated by Parp1 and its substrate NAD and require an intact macrodomain capable of binding poly(ADP-ribose). Alc1 is rapidly recruited to nucleosomes in vitro and to chromatin in cells when Parp1 catalyzes PAR synthesis. We propose that poly(ADP-ribosyl)ation of chromatin-associated Parp1 serves as a mechanism for targeting a SNF2 family remodeler to chromatin.

| S-EPMC2722505 | biostudies-literature

The INO80 ATP-dependent chromatin remodeling complex is a nucleosome spacing factor.

Project description:The mobilization of nucleosomes by the ATP-dependent remodeler INO80 is quite different from another remodeler (SWI/SNF) that is also involved in gene activation. Unlike that recently shown for SWI/SNF, INO80 is unable to disassemble nucleosomes when remodeling short nucleosomal arrays. Instead, INO80 more closely resembles, although with notable exceptions, the nucleosome spacing activity of ISW2 and ISW1a, which are generally involved in transcription repression. INO80 required a minimum of 33 to 43 bp of extranucleosomal DNA for mobilizing nucleosomes, with 70 bp being optimal. INO80 prefers to move mononucleosomes to the center of DNA, like ISW2 and ISW1a, but does so with higher precision. Unlike ISW2/1a, INO80 does not require the H4 tail for nucleosome mobilization; instead, the H2A histone tail negatively regulates nucleosome movement by INO80. INO80 moved arrays of two or three nucleosomes with 50 or 79 bp of linker DNA closer together, with a final length of ?30 bp of linker DNA or a repeat length of ?177 bp. A minimum length of >30 bp of linker DNA was required for nucleosome movement and spacing by INO80 in arrays.

| S-EPMC3028646 | biostudies-literature

Replication-Coupled Nucleosome Assembly and Positioning by ATP-Dependent Chromatin-Remodeling Enzymes.

Project description:During DNA replication, chromatin must be disassembled and faithfully reassembled on newly synthesized genomes. The mechanisms that govern the assembly of chromatin structures following DNA replication are poorly understood. Here, we exploited Okazaki fragment synthesis and other assays to study how nucleosomes are deposited and become organized in S. cerevisiae. We observe that global nucleosome positioning is quickly established on newly synthesized DNA in vivo. Importantly, we find that ATP-dependent chromatin-remodeling enzymes, Isw1 and Chd1, collaborate with histone chaperones to remodel nucleosomes as they are loaded behind a replication fork. Using a whole-genome sequencing approach, we determine that the positioning of newly deposited nucleosomes in vivo is specified by the combined actions of ATP-dependent chromatin-remodeling enzymes and select DNA-binding proteins. Altogether, our data provide in vivo evidence for coordinated "loading and remodeling" of nucleosomes behind the replication fork, allowing for rapid organization of chromatin during S phase.

| S-EPMC5063657 | biostudies-literature

Dinucleosome specificity and allosteric switch of the ISW1a ATP-dependent chromatin remodeler in transcription regulation.

Project description:Over the last 3 decades ATP-dependent chromatin remodelers have been thought to recognize chromatin at the level of single nucleosomes rather than higher-order organization of more than one nucleosome. We show the yeast ISW1a remodeler has such higher-order structural specificity, as manifested by large allosteric changes that activate the nucleosome remodeling and spacing activities of ISW1a when bound to dinucleosomes. Although the ATPase domain of Isw1 docks at the SHL2 position when ISW1a is bound to either mono- or di-nucleosomes, there are major differences in the interactions of the catalytic subunit Isw1 with the acidic pocket of nucleosomes and the accessory subunit Ioc3 with nucleosomal DNA. By mutational analysis and uncoupling of ISW1a's dinucleosome specificity, we find that dinucleosome recognition is required by ISW1a for proper chromatin organization at promoters; as well as transcription regulation in combination with the histone acetyltransferase NuA4 and histone H2A.Z exchanger SWR1.

| S-EPMC7680125 | biostudies-literature

The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution

Project description:We addressed the roles of primarily two remodeling complexes, ISW1a and ISW1b, in affecting the chromatin organization in the yeast Saccharomyces cerevisiae.

2021-02-02 | GSE156224 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data