Which Two Nucleosome Remodeling Models Exist?

Nucleosomes are dynamic nucleoprotein complexes involved in almost every genomic process. Chromatin remodellers, helicase-like, ATP-dependent enzymes, alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. These remodelers can be grouped into two classes: nucleosome translocation enzymes that move histone octamers along DNA, and histone exchange factors that physically reposition nucleosomes along DNA.

There are two types of chromatin remodeling (CR): one initiated by various types of histone modification and the other by ATP-dependent mobilization of nucleosomes, which is called nucleosome remodelling (NR). ATP-dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. Two models are proposed to explain nucleosome sliding – Twist diffusion and Loop/bulge propagation. Both models suggest that DNA distortion propagates over the surface of the nucleosome, with a single base pair being transferred between linked DNA and the DNA wrapped around the histone core.

The consequences of ATP-dependent nucleosome remodeling include changes in the position or composition of chromatin. Two closely related RSC members, Rsc1 and Rsc2, have been identified and biochemically identified in distinct complexes, defining two forms of RSC. The end product of the chromatin is a conserved ATP-dependent chromatin remodeling complex that regulates many biological processes.

In summary, nucleosomes are highly dynamic nucleoprotein complexes involved in almost every genomic process. Chromatin remodellers are ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA.

What are the different types of chromatin remodeling complexes?

Chromatin remodeling is a crucial process in eukaryotes, involving four families: SWI/SNF, ISWI, NuRD /Mi-2/ CHD, and INO80. These remodelers share a common ATPase domain but have unique protein domains and recruited subunits. ISWI remodelers organize nucleosomes into proper bundle form, while SWI/SNF remodelers disorder nucleosomes. ISWI-family remodelers play central roles in chromatin assembly after DNA replication and maintenance of higher-order chromatin structures.

INO80 and SWI/SNF-family remodelers participate in DNA double-strand break repair and nucleotide-excision repair, playing a crucial role in TP53-mediated DNA damage response. NuRD/Mi-2/ CHD remodeling complexes mediate transcriptional repression in the nucleus and are required for embryonic stem cell pluripotency maintenance. Chromatin remodeling regulates gene expression by providing dynamic access to the genome.

Nucleosome movement by chromatin remodelers is essential for chromosome assembly, DNA replication, embryonic development, pluripotency, and cell-cycle progression. Deregulation of chromatin remodeling leads to loss of transcriptional regulation at critical check-points, leading to various disease syndromes, including cancer.

What are 2 roles of nucleosomes?

Nucleosomes are the basic packing unit of genomic DNA, built from histone proteins. They serve as a scaffold for higher order chromatin structure and a layer of regulatory control of gene expression. Nucleosomes are assembled onto newly synthesized DNA behind the replication fork. Disassembled old nucleosomes’ histones H3 and H4 are kept in the vicinity and randomly distributed on the newly synthesized DNA. The chromatin assembly factor 1 (CAF-1) complex assembles these proteins, while the replication coupling assembly factor (RCAF) assembles newly synthesized H3 and H4 proteins.

The old H3 and H4 proteins retain their chemical modifications, contributing to the passing down of the epigenetic signature. The newly synthesized H3 and H4 proteins are gradually acetylated at different lysine residues as part of the chromatin maturation process. The old H3 and H4 proteins in the new nucleosomes recruit histone modifying enzymes that mark the new histones, contributing to epigenetic memory.

Newly assembled H2A and H2B histone proteins are incorporated into new nucleosomes, assembled into dimers and loaded onto nucleosomes by the nucleosome assembly protein-1 (NAP-1). Nucleosomes are also spaced by ATP-dependent nucleosome-remodeling complexes containing enzymes such as Isw1, Ino80, and Chd1, and subsequently assembled into higher order structure.

What is the nucleosome model?

The nucleosome model, proposed by R. D. Kornberg in 1974, explains the structure of nucleosomes by wrapping a histone particle with DNA. This model was confirmed by P. Oudet in 1975. Scientists discovered the interaction between DNA and histones in chromatin through the separation of chromatin samples on an agarose gel. They found that DNA forms fragments of approximately 200 base pairs or multiples of 200 bps, suggesting DNA is protected from the nuclease enzyme at specific points along its length. Proteins (histones) interacting with DNA in chromatin provide this type of protection, leading to the nucleosome model of chromatin organization.

How are nucleosomes remodeled?

Nucleosome remodeling involves the movement of DNA segments from the histone octamer surface, which is facilitated by the ATPase domains of all known nucleosome remodelers. These remodelers are related to the larger superfamily of nucleic acid helicases and have been found to be DNA translocases. They engage in other defined contacts with histones and linker DNA, positioning the ATPase domain at a strategic site within the nucleosomal DNA.

This anchoring, combined with the translocation of the ATPase domain on nucleosomal DNA, leads to the detachment of DNA segments from the histone octamer surface. Cycles of ATP binding, hydrolysis, and product release define a succession of conformation changes of the enzyme, propelling the movement of the enzyme on DNA.

The precise mechanism of nucleosome remodeling is currently lacking, but it is likely that the precise mechanism will differ for each of the individual remodeling ATPases, depending on enzyme structure and geometry, the arrangement, affinities, and selectivity of histone and DNA interaction domains, including the translocase domain itself. Electron microscopy studies have generated structures of the Swi/Snf complex and the related RSC complex, which resemble the Swi/Snf complex in subunit composition and overall architecture.

The structure of the RSC complex bound to a nucleosome is particularly insightful, revealing that RSC engulfs the nucleosome within a central cavity. Importantly, ATP-independent binding of RSC to the nucleosome appears to alter histone–DNA interactions perhaps to facilitate ATP-dependent remodeling. Nucleosomal DNA within the structure appears relatively unconstrained by the complex and may be able to undergo movement of the kinds described above.

RSC-nucleosome complexes have been found in vivo, such as at the yeast UASg locus, where RSC positions an apparently partially unwound nucleosome to facilitate transcription factor binding to nearby sites.

The nucleosome view of the nucleosome core shows the left-hand wrapping of DNA, with the histone octamer represented as a gray transparent cylinder and the DNA in orange (before the dyad axis) and red (after the dyad axis). A model for DNA movement across the histone octamer during remodeling event by ISWI-type enzymes is presented. State I involves the DNA binding domain (DBD) being bound to the linker DNA and the translocase (Tr) domain being bound near the nucleosome dyad.

In State II, a conformational change between the DBD and the Tr “pulls in” DNA, which becomes visible as a bulge on the histone octamer surface. The Tr activity propagates this bulge across the surface of the histone octamer beyond the dyad axis (State III). The DNA loop continues to diffuse across the octamer surface and is released into the distal linker DNA (State IV). Loop diffusion effectively repositions the histone octamer relative to the DNA sequence (i.

E., the star has moved closer to the dyad axis). A further conformational change triggered by aspects of the ATPase cycle lead to a resetting of the remodeler relative to the histone octamer (compare in States IV and I).

Cryo-electron microscopy (EM) analysis of the RSC structure and nucleosome interaction shows that the yeast RSC resembles the Swi/Snf complex in subunit composition and overall architecture. Instead of the ATPase Swi2/Snf2, it contains the Sth1ATPase, which belongs to the same subfamily. A 25-Å cryo-EM map of RSC shows a central cavity that closely matches the shape and dimensions of a nucleosome core particle. Incubation of RSC with nucleosome core particles (NCPs) results in the formation of a RSC-NCP complex, with NCP density apparent in the central RSC cavity.

Interestingly, interaction with RSC in the absence of any ATP hydrolysis appears to result in extensive changes in NCP organization. This loosening of DNA may facilitate DNA translocation during remodeling.

The classification of the many SNF2-type ATPases into subfamilies rests on sequence features within the ATPase domain, but the more closely related ATPases also share particular domains and sequence signatures outside of the ATPase domains.

What are two components of a nucleosome?

The nucleosome structure is composed of DNA and a histone protein complex, with a single DNA strand coiled around a core histone octamer.

What is the name of one major molecular complex that remodels nucleosomes?

Nucleosome remodeling and histone variant incorporation are primarily achieved through ATP-dependent chromatin remodeling complexes, which are grouped into SWI/SNF, ISWI, CHD, or INO80 sub-families based on sequence homology of the associated ATPase. NURF, a crucial component of the chromatin remodeling machinery, is a founding member of the ISWI family. It plays a vital role in chromatin biology, regulating transcription, establishing boundary elements, and promoting higher order chromatin structure.

Understanding NURF’s function is crucial for understanding genome regulation. This review summarizes its biological functions, conservation in model organisms, biochemical functions as a nucleosome remodeling enzyme, and its potential relevance to human cancer.

What are the two types of chromatin modification?

The text explains the various modifications and functions of chromatoin, residues, and transcription, including arginine methylation, phosphorylation, sulfonylation, and phosphorylation. It also mentions the use of cookies on the site and the copyright © 2024 Elsevier B. V., its licensors, and contributors. All rights reserved for text and data mining, AI training, and similar technologies.

What are chromatin remodeling complexes?

Chromatin remodelers are large multiprotein complexes that utilize the energy derived from the hydrolysis of adenosine triphosphate (ATP) to mobilize and restructure nucleosomes.

What is the zigzag model of nucleosomes?

Coarse-grained oligonucleosome models, such as zigzag and solenoid fiber models, have been studied for their impact on chromatin compaction. Zigzag models propose two-start fibers with two nucleosomes at the start, where linker DNA crosses the main fiber axis. In these models, nucleosomes are stacked in the periphery of the fiber, and linker DNA occupies the central space of the structure. Solenoid models propose compaction through coiling of the linker DNA along the superhelical path, with fibers being one-start and nucleosomes creating frontal contacts. Both models coexist in fibers, along with straight and bent linker DNA.

Different nucleosome repeat lengths (NRL) also influence fiber configurations and the propensity of a fiber to unfold. Monte Carlo (MC) simulations were performed on coarse-grained oligonucleosome fibers, revealing that structures with highly varying NRL were more compact than uniform structures due to fewer topological constraints. Transcriptionally active cells presented shorter NRLs, while inactive cells had the opposite effect. Shorter NRL fibers were arranged in ladder-like forms in the coarse-grained model, while medium fibers arranged in zig-zags and longer NRLs resulted in heteromorphic structures.

Nucleosomes bearing histone modifications, or even less histones than the canonic octamer, have also been studied as a factor influencing chromatin compaction. Full atom models are very instructive in the mononucleosome scale, but in mesoscale chromatin models, DNA base pairs are represented as rigid bodies with parameters accounting for orientation and displacement. More coarse-grained models often treat nucleosomes as rigid bodies with concentrated charge, and the dynamics of histone tails are modeled as Gaussian distributions or series of beads.

What is the nucleosome model and solenoid model?

The solenoid model posits that nucleosomal DNA forms a superhelix with six nucleosomes per turn, exhibiting a helical pitch of 11 nm and a 30-nm fiber constituted by nucleosome discs.

What are the two types of histones?

Histones are divided into two classes: core histones and linker histones. Core histones consist of four members: H2A, H2B, H3, and H4. Linker histones include H1 or its homologue H5. Core histones are synthesized during DNA replication and reach peak expression in the S phase. They have a strong conservation across species, from yeast to humans. Core histones have a C-terminal histone-fold domain (HFD) involved in histone octamer formation and an unstructured N-terminal tail subjected to post-translational modifications.

Within a nucleosome, core histones form an octamer with 147 bp of DNA spooled twice. The interaction between H1 and the nucleosome and additional DNA stretches results in the formation of the beads-on-a-string chromosome and higher-order chromatin structure.