# Nucleosome Formation: Mechanisms and Structural Insights

## Introduction to Nucleosome Formation

The nucleosome is the fundamental repeating unit of chromatin, the complex of DNA and proteins that packages the eukaryotic genome within the nucleus. Each nucleosome consists of approximately 147 base pairs (bp) of DNA wrapped around a histone octamer core, forming a structure that resembles a bead on a string when viewed under low-resolution microscopy. This packaging is not merely a storage solution; it is a dynamic regulatory platform that governs DNA accessibility for essential processes including transcription, replication, repair, and recombination.

The formation of a nucleosome is a carefully orchestrated process that involves the ordered assembly of histone proteins around DNA. Understanding nucleosome formation is critical because the positioning and density of nucleosomes along the genome directly influence gene expression patterns. Regions of chromatin that are densely packed with nucleosomes are generally transcriptionally silent, while nucleosome-free regions or those with unstable nucleosomes are accessible to [transcription factors](/knowledge/molecular-biology/transcription-factor) and RNA polymerase. Furthermore, nucleosome formation is intimately linked to DNA replication, as the entire genome must be repackaged into chromatin after each round of DNA synthesis.

### The [Nucleosome Core Particle](/knowledge/molecular-biology/nucleosome-core-particle)

The [nucleosome core particle](/knowledge/molecular-biology/nucleosome-core-particle) (NCP) is the structural heart of chromatin. It comprises the histone octamer—two copies each of histones H2A, H2B, H3, and H4—and the 147 bp of DNA that wraps around it. The DNA makes approximately 1.65 superhelical turns around the octamer, creating a left-handed superhelix. The overall dimensions of the NCP are roughly 11 nm in diameter and 5.5 nm in height, making it a compact yet remarkably dynamic structure.

The interface between DNA and the histone octamer is extensive. Each histone protein contributes to the binding of DNA through electrostatic interactions between the positively charged lysine and arginine residues on the histones and the negatively charged phosphate backbone of DNA. Additionally, nonpolar contacts and hydrogen bonds stabilize the interaction. The periodic bending of DNA around the octamer is facilitated by the intrinsic flexibility of the DNA double helix, which is enhanced by the sequence-dependent deformability of certain dinucleotide steps.

### Histone Proteins and DNA Wrapping

Histones are small, highly basic proteins that are among the most conserved proteins in eukaryotes. The core histones (H2A, H2B, H3, and H4) share a common structural motif known as the histone fold domain, which mediates histone-histone interactions within the octamer. Each histone also possesses an unstructured N-terminal tail that extends outward from the nucleosome core. These tails are subject to a wide array of post-translational modifications, including acetylation, methylation, phosphorylation, and ubiquitination, which modulate chromatin structure and function.

The wrapping of DNA around the histone octamer is not uniform. The DNA is most tightly associated with the octamer at the superhelix locations where it contacts the histone fold domains, while the entry and exit points of the DNA are more dynamic. This differential binding is functionally significant, as it allows for the regulated unwrapping of DNA ends during processes such as transcription factor binding and RNA polymerase passage.

## The Histone Octamer and DNA Wrapping

### Histone Fold Domains

The histone fold domain is a conserved structural element consisting of three alpha-helices (α1, α2, and α3) connected by two loops (L1 and L2). This domain enables the heterodimerization of histones in a specific "handshake" arrangement. H3 pairs with H4 to form the H3-H4 dimer, and H2A pairs with H2B to form the H2A-H2B dimer. These dimers are the building blocks of the histone octamer.

The H3-H4 dimers associate to form a tetramer through a four-helix bundle involving the α2 and α3 helices of the two H3 molecules. This (H3-H4)₂ tetramer forms the central scaffold of the nucleosome, binding the central 60-70 bp of DNA. The two H2A-H2B dimers then dock onto the tetramer, one on each face, through interactions between the H2B and H4 histone folds and the H2A and H3 regions. The final octamer is a tripartite structure with a central (H3-H4)₂ tetramer flanked by two H2A-H2B dimers.

The histone fold domains are not only structural elements; they also create the positively charged surface that interacts with DNA. The L1 and L2 loops, along with the α1 helices, form a series of arginine side chains that penetrate the minor groove of DNA at regular intervals. These arginine "fingers" make sequence-independent contacts with the DNA backbone, providing the majority of the binding energy that stabilizes the nucleosome.

### DNA-Histone Contacts

The 147 bp of DNA in the nucleosome core makes contact with the histone octamer at 14 distinct sites, each separated by approximately one helical turn (10 bp). At each site, the DNA minor groove faces inward toward the histone surface, and an arginine residue from one of the histones inserts into the minor groove. These arginine residues are highly conserved and are essential for nucleosome stability.

The DNA is bent sharply around the octamer, with an average bend radius of about 4.5 nm. This bending is facilitated by the flexibility of the DNA backbone, particularly at TA and AA dinucleotide steps, which are more deformable than GC steps. The sequence of the DNA therefore influences nucleosome positioning: sequences that contain periodic distributions of flexible dinucleotides at positions where the minor groove faces the histone surface are more favorable for nucleosome formation.

The total buried surface area at the DNA-histone interface is approximately 3,200 Ų per nucleosome. The interaction is dominated by electrostatic contacts between the positively charged histone residues and the negatively charged DNA phosphate groups. However, the overall binding affinity is modulated by the ionic environment. In vitro, nucleosome formation is highly dependent on salt concentration: at physiological ionic strength (150 mM NaCl), nucleosomes are stable, but at high salt concentrations (above 1 M NaCl), the histones dissociate from DNA.

## Stepwise Assembly of the Nucleosome

Nucleosome formation in vivo is not a spontaneous process; it is mediated by histone chaperones and assembly factors that ensure the correct order of histone deposition and prevent non-specific aggregation of histones with DNA. The assembly pathway is ordered and involves the sequential addition of histone complexes to DNA.

### H3-H4 Tetramer Deposition

The first step in nucleosome formation is the deposition of the (H3-H4)₂ tetramer onto DNA. This tetramer binds to the central region of the nucleosomal DNA, establishing the translational position of the nucleosome. The tetramer makes extensive contacts with the central 60-70 bp of DNA, bending it around the nascent nucleosome core.

Histone chaperones such as CAF-1 (chromatin assembly factor 1) and Asf1 (anti-silencing function 1) facilitate this deposition. CAF-1 is a trimeric complex (p150, p60, and p48 subunits in humans) that specifically associates with the DNA polymerase sliding clamp PCNA during replication, coupling nucleosome assembly to DNA synthesis. Asf1, on the other hand, binds to the H3-H4 dimer and delivers it to CAF-1 or to the HIRA (histone regulatory homolog A) complex for replication-independent assembly.

The deposition of the tetramer is the rate-limiting step in nucleosome formation. Once the tetramer is in place, the subsequent addition of H2A-H2B dimers occurs more rapidly. The tetramer also establishes the periodicity of DNA wrapping, as the arginine residues of H3 and H4 insert into the minor groove at defined intervals.

### H2A-H2B Dimer Addition

Following tetramer deposition, two H2A-H2B dimers are added, one to each side of the tetramer. These dimers bind to the DNA at the entry and exit points of the nucleosome, completing the 1.65 superhelical turns. The addition of H2A-H2B dimers stabilizes the nucleosome and locks the DNA into its wrapped conformation.

The chaperone Nap1 (nucleosome assembly protein 1) is a key factor in H2A-H2B deposition. Nap1 binds to the H2A-H2B dimer and delivers it to the tetrasome (the DNA-(H3-H4)₂ complex). The binding of Nap1 to H2A-H2B prevents the dimer from interacting non-specifically with DNA, which would lead to aggregation. Nap1 also plays a role in the removal of H2A-H2B dimers during transcription, highlighting its dual function in assembly and disassembly.

The ordered assembly pathway ensures that the nucleosome is formed with the correct stoichiometry and that the DNA is wrapped with the proper geometry. Errors in this process can lead to the formation of non-canonical nucleosomes, such as hemisomes (containing one copy of each histone) or nucleosomes with incorrect histone stoichiometry, which can have deleterious effects on genome stability.

## Histone Chaperones and Assembly Factors

Histone chaperones are a diverse group of proteins that bind histones and facilitate their incorporation into nucleosomes. They are not part of the final nucleosome structure but are essential for its formation. Chaperones prevent the non-specific aggregation of histones with DNA, which would otherwise occur due to the strong electrostatic attraction between the positively charged histones and negatively charged DNA.

### Replication-Coupled Assembly

During S phase, the genome must be duplicated and the newly synthesized DNA must be packaged into chromatin. This process, termed replication-coupled nucleosome assembly, is mediated by the coordinated action of several chaperones. CAF-1 is the primary chaperone responsible for depositing H3-H4 onto newly replicated DNA. It interacts with PCNA, which is loaded onto the DNA at replication forks, ensuring that nucleosome assembly occurs immediately behind the replication machinery.

The newly synthesized H3-H4 dimers are acetylated at specific lysine residues (e.g., H3K56ac in yeast, H4K5ac and H4K12ac in humans) before they are incorporated into nucleosomes. These acetylation marks are recognized by chaperones and are removed by deacetylases after assembly. The acetylation of new histones is thought to facilitate their deposition by reducing their affinity for DNA, allowing the chaperones to control the assembly process.

The recycling of parental histones is also an important aspect of replication-coupled assembly. Parental H3-H4 tetramers are transferred from the parental DNA to the daughter strands, preserving the epigenetic marks carried by these histones. The chaperone FACT (facilitates chromatin transcription) has been implicated in this process, as it can bind to H3-H4 and H2A-H2B and facilitate their transfer.

### Transcription-Coupled Assembly

Nucleosome formation also occurs during transcription, when RNA polymerase traverses the DNA template and displaces nucleosomes. The FACT complex plays a central role in this process. FACT is a heterodimer of Spt16 and SSRP1 in humans, and it binds to H2A-H2B dimers, promoting their removal from the nucleosome ahead of the polymerase and their re-deposition behind it. FACT does not hydrolyze ATP; instead, it destabilizes the nucleosome by altering the H2A-H2B-DNA interactions, allowing the polymerase to pass.

The HIRA chaperone complex is responsible for replication-independent nucleosome assembly, which occurs at sites of DNA damage and in regions of active transcription. HIRA deposits H3.3, a histone variant that is enriched in actively transcribed genes and at regulatory elements. The deposition of H3.3 by HIRA is coupled to transcription and is thought to maintain chromatin integrity in regions that undergo frequent nucleosome turnover.

## Energetics and Dynamics of Nucleosome Formation

The formation of a nucleosome is thermodynamically favorable under physiological conditions, but the free energy change is modest. The binding of DNA to the histone octamer is driven by the release of counterions and water molecules from the DNA and histone surfaces. When DNA is free in solution, its phosphate backbone is surrounded by a cloud of cations (primarily Na⁺ and Mg²⁺) and water molecules. When the DNA wraps around the histone octamer, these ions and water molecules are released, resulting in a favorable increase in entropy.

### DNA Bending and Supercoiling

The wrapping of DNA around the histone octamer introduces a severe bend in the DNA. The free energy cost of bending DNA is significant, estimated to be approximately 1 kcal/mol per 10 bp for a bend of the magnitude found in the nucleosome. This cost is offset by the favorable electrostatic interactions between the histones and DNA, as well as by the entropic gain from counterion release.

The wrapping of DNA around the octamer also introduces negative supercoiling. In the nucleosome, the DNA is wrapped in a left-handed superhelix, which corresponds to approximately -1.65 superhelical turns per nucleosome. This negative supercoiling is important for processes such as transcription, where the unwinding of the DNA double helix by RNA polymerase generates positive supercoiling ahead of the polymerase and negative supercoiling behind it. The presence of nucleosomes can modulate these topological changes.

The stability of the nucleosome is influenced by the ionic strength of the environment. In vitro, nucleosomes are stable at NaCl concentrations between 100 mM and 600 mM. Below 100 mM NaCl, the nucleosome becomes less stable due to increased electrostatic repulsion between the DNA and histones, while above 600 mM, the histones begin to dissociate. The optimal salt concentration for nucleosome reconstitution in vitro is approximately 2 M NaCl, followed by gradual dialysis to lower salt concentrations.

### Histone Variants and Modifications

Histone variants add another layer of complexity to nucleosome formation. H3.3, mentioned earlier, differs from the canonical H3 by only a few amino acids but is deposited by HIRA in a replication-independent manner. The centromere-specific variant CENP-A (in humans) replaces H3 in centromeric nucleosomes and is essential for kinetochore assembly. The H2A variants H2A.X and H2A.Z have specialized functions in DNA damage response and gene regulation, respectively. These variants can alter nucleosome stability and dynamics, influencing chromatin structure and function.

Post-translational modifications of histone tails can also affect nucleosome formation and stability. Acetylation of lysine residues on the N-terminal tails of H3 and H4 neutralizes the positive charge of these residues, reducing their affinity for DNA. This can destabilize the nucleosome and promote chromatin decondensation. Methylation of lysine and arginine residues does not change the charge but can recruit proteins that either compact or decompact chromatin. Phosphorylation of serine and threonine residues introduces negative charges, which can also affect nucleosome stability.

The role of histone modifications in nucleosome formation is distinct from their role in [chromatin remodeling](/knowledge/molecular-biology/chromatin-remodeling). Modifications do not directly assemble or disassemble nucleosomes; rather, they modulate the affinity of histones for DNA and serve as docking sites for chromatin-associated proteins. For example, acetylation of H4K16 has been shown to inhibit the compaction of chromatin fibers by reducing the interaction between the H4 tail and the acidic patch of adjacent nucleosomes.

## Methods to Study Nucleosome Formation

The study of nucleosome formation has been greatly advanced by the development of in vitro reconstitution systems and high-resolution structural techniques. These methods allow researchers to dissect the molecular mechanisms of nucleosome assembly and to determine the effects of histone modifications, variants, and chaperones on nucleosome stability.

### In Vitro Reconstitution Assays

The most common method for studying nucleosome formation in vitro is the salt dialysis method. In this approach, purified histone octamers and DNA are mixed in a high-salt buffer (typically 2 M NaCl) and then gradually dialyzed against buffers of decreasing salt concentration. As the salt concentration drops, the histones bind to the DNA and assemble into nucleosomes. The efficiency of reconstitution can be assessed by [native polyacrylamide gel electrophoresis](/knowledge/diagnostics/molecular/native-polyacrylamide-gel-electrophoresis) (PAGE), where nucleosomes migrate more slowly than free DNA.

A key advantage of the salt dialysis method is that it allows for the incorporation of specific histone variants or modified histones into the nucleosome. Histones can be expressed recombinantly in bacteria, purified, and then assembled into octamers. Post-translational modifications can be introduced either by chemical ligation or by using enzymes that add specific modifications. This approach has been used to determine the effects of individual modifications on nucleosome stability and dynamics.

Another powerful technique is the histone chaperone-mediated assembly assay. In this assay, histones are incubated with a chaperone such as Nap1 or CAF-1, and the complex is then added to DNA. The assembly reaction is monitored by native PAGE or by a supercoiling assay, where the formation of nucleosomes on a relaxed plasmid DNA introduces negative supercoils that can be detected by agarose gel electrophoresis in the presence of chloroquine.

### Single-Molecule Approaches

Single-molecule techniques have provided unprecedented insights into the dynamics of nucleosome formation. Optical tweezers can be used to measure the force required to unwrap DNA from the histone octamer. These experiments have shown that the outer turn of DNA (the DNA at the entry and exit points) unwraps more readily than the inner turn, and that the unwrapping occurs in discrete steps corresponding to the breaking of individual DNA-histone contacts.

Fluorescence resonance energy transfer (FRET) has been used to monitor the assembly of nucleosomes in real time. By labeling the DNA and histones with donor and acceptor fluorophores, researchers can observe the stepwise wrapping of DNA around the histone octamer. These studies have revealed that nucleosome formation is a multi-step process, with an initial rapid binding of the H3-H4 tetramer followed by the slower addition of H2A-H2B dimers.

Atomic force microscopy (AFM) and cryo-electron microscopy (cryo-EM) have provided high-resolution structures of nucleosomes and their assembly intermediates. Cryo-EM has been particularly valuable, as it allows for the determination of structures of nucleosomes in complex with chaperones and remodelers at near-atomic resolution. These structures have revealed the conformational changes that occur during nucleosome assembly and have identified the specific contacts between chaperones and histones.

## Nucleosome Formation in Vivo: Chromatin Assembly

In vivo, nucleosome formation is tightly coordinated with DNA replication, transcription, and repair. The assembly of chromatin is not a passive process; it is actively regulated by a network of chaperones, remodelers, and modifying enzymes that ensure the correct packaging of the genome.

### Replication-Coupled Nucleosome Assembly

During DNA replication, the parental nucleosomes are disrupted ahead of the replication fork, and the newly synthesized DNA must be rapidly packaged into nucleosomes. This process is initiated by the loading of CAF-1 onto PCNA at the replication fork. CAF-1 then deposits (H3-H4)₂ tetramers onto the newly synthesized DNA, followed by the addition of H2A-H2B dimers, which is mediated by Nap1 or other chaperones.

The assembly of nucleosomes during replication is not random. The newly synthesized histones are acetylated at specific residues, which is thought to mark them as "new" and to facilitate their deposition. The parental histones, which carry the epigenetic marks that define the chromatin state of a region, are recycled and distributed to the daughter strands. The mechanism of parental histone recycling is not fully understood, but it is known to involve the transfer of H3-H4 tetramers as intact units, while H2A-H2B dimers are exchanged more freely.

The speed of nucleosome assembly during replication is remarkable. In yeast, the replication fork moves at approximately 1.5-2 kb per minute, and nucleosomes are assembled on the newly synthesized DNA within seconds of fork passage. This rapid assembly is essential for maintaining genome stability, as naked DNA is more susceptible to damage and aberrant recombination.

### Nucleosome Assembly in Transcription

Nucleosome formation also occurs during transcription, where the passage of RNA polymerase disrupts nucleosomes. The FACT complex plays a central role in this process by facilitating the removal of H2A-H2B dimers from the nucleosome ahead of the polymerase and their re-deposition behind it. FACT does not assemble nucleosomes from scratch; instead, it promotes the exchange of H2A-H2B dimers, allowing the polymerase to traverse the nucleosome without completely disassembling it.

In addition to FACT, the histone chaperone Spt6 has been shown to play a role in transcription-coupled nucleosome assembly. Spt6 binds to the phosphorylated C-terminal domain of RNA polymerase II and deposits H3-H4 tetramers onto the DNA behind the polymerase. This deposition is important for maintaining chromatin integrity during transcription and for preventing the initiation of cryptic transcription from within gene bodies.

The assembly of nucleosomes during transcription is also influenced by histone modifications. The acetylation of H3K56, which is deposited on new histones during replication, is also added to histones during transcription. This modification is recognized by the chaperone Rtt106 in yeast, which facilitates the deposition of H3-H4 tetramers. The removal of H3K56 acetylation by deacetylases after assembly is important for maintaining genome stability.

## Common Pitfalls and Misconceptions

Students often encounter several conceptual difficulties when learning about nucleosome formation. These misconceptions can lead to errors in exams and in the application of concepts to research problems.

### Nucleosome vs. Chromatosome

A common error is to confuse the nucleosome with the chromatosome. The nucleosome core particle consists of 147 bp of DNA wrapped around the histone octamer. The chromatosome, on the other hand, includes the nucleosome core plus an additional 20-40 bp of linker DNA bound to a linker histone, such as H1. The linker histone binds to the entry and exit points of the DNA on the nucleosome and stabilizes the higher-order folding of chromatin. While the nucleosome is the fundamental repeating unit of chromatin, the chromatosome is a more complete structural unit that includes the linker histone.

### [Histone Modification](/knowledge/molecular-biology/histone-modification) vs. Assembly

Another common misconception is that histone modifications are required for nucleosome assembly. While some modifications, such as acetylation of H3K56 and H4K16, are associated with newly synthesized histones and may facilitate their deposition, the core process of nucleosome formation does not require any specific modification. In vitro, nucleosomes can be assembled from unmodified histones and DNA using the salt dialysis method. Histone modifications play a regulatory role, modulating the stability of nucleosomes and serving as signals for the recruitment of chromatin-associated proteins, but they are not essential for the basic assembly process.

Students also sometimes confuse nucleosome formation with [chromatin remodeling](/knowledge/molecular-biology/chromatin-remodeling). Nucleosome formation is the assembly of the nucleosome from histones and DNA. Chromatin remodeling, in contrast, refers to the ATP-dependent movement or ejection of nucleosomes by remodeling complexes such as SWI/SNF and RSC. Remodelers do not assemble nucleosomes; they alter the position or composition of existing nucleosomes. The distinction is important because the two processes are mediated by different protein complexes and serve different functions.

A further misconception is that nucleosome formation requires ATP. In fact, the basic assembly of nucleosomes from histones and DNA is ATP-independent. The energy for nucleosome formation comes from the favorable electrostatic interactions and entropic effects described earlier. ATP is required for chromatin remodeling, which involves the movement of nucleosomes along DNA, but not for the initial assembly of the nucleosome. In vivo, ATP is also required for the activity of chaperones such as CAF-1, which use ATP to facilitate the deposition of histones, but the nucleosome itself can form without ATP.

## Frequently Asked Questions

### What is the order of histone assembly in nucleosome formation?

The assembly of the nucleosome follows an ordered pathway. First, an H3-H4 tetramer, (H3-H4)₂, is deposited onto DNA, binding to the central region of the nucleosomal DNA. This is followed by the addition of two H2A-H2B dimers, one on each side of the tetramer. The H3-H4 tetramer establishes the translational position of the nucleosome, while the H2A-H2B dimers complete the wrapping of DNA around the octamer.

### How many base pairs of DNA wrap around a nucleosome?

The nucleosome core particle contains 147 base pairs of DNA. This DNA makes 1.65 superhelical turns around the histone octamer. If the linker DNA between nucleosomes is included, the total repeat length in most eukaryotes is approximately 180-200 bp, but the core particle is defined as 147 bp.

### What are histone chaperones and why are they important?

Histone chaperones are proteins that bind to histones and facilitate their incorporation into nucleosomes. They are important because they prevent the non-specific aggregation of histones with DNA, which would occur due to the strong electrostatic attraction between the positively charged histones and negatively charged DNA. Chaperones also ensure the correct order of histone deposition and couple nucleosome assembly to processes such as DNA replication and transcription.

### What is the difference between nucleosome formation and chromatin remodeling?

Nucleosome formation is the assembly of nucleosomes from histones and DNA. Chromatin remodeling is the ATP-dependent movement, ejection, or exchange of nucleosomes by remodeling complexes such as SWI/SNF. Nucleosome formation does not require ATP, while chromatin remodeling does. The two processes are mediated by different protein complexes and serve distinct functions.

### How is nucleosome formation studied in the lab?

Nucleosome formation is commonly studied using in vitro reconstitution assays, where purified histones and DNA are mixed in high salt and then dialyzed to lower salt concentrations. The efficiency of assembly is assessed by native PAGE or supercoiling assays. Single-molecule techniques such as optical tweezers and FRET are used to study the dynamics of nucleosome assembly, and cryo-EM is used to determine high-resolution structures of nucleosomes and assembly intermediates.

### What role do histone modifications play in nucleosome formation?

Histone modifications are not required for the basic process of nucleosome formation, but they can modulate nucleosome stability and serve as signals for the recruitment of chaperones and other chromatin-associated proteins. For example, acetylation of H3K56 and H4K16 on newly synthesized histones is thought to facilitate their deposition during replication. Other modifications, such as methylation and phosphorylation, can affect nucleosome stability and chromatin compaction.

### Does nucleosome formation require ATP?

No, the basic assembly of nucleosomes from histones and DNA does not require ATP. The process is driven by electrostatic interactions and entropic effects. ATP is required for chromatin remodeling, which involves the movement of nucleosomes along DNA, and for the activity of some chaperones that facilitate histone deposition in vivo.

## Key Takeaways

- The nucleosome is the fundamental repeating unit of chromatin, consisting of 147 bp of DNA wrapped around a histone octamer (two copies each of H2A, H2B, H3, and H4) in 1.65 superhelical turns.
- Nucleosome formation is an ordered process: the (H3-H4)₂ tetramer is deposited first, followed by two H2A-H2B dimers.
- Histone chaperones such as CAF-1, Asf1, Nap1, and FACT prevent non-specific histone-DNA aggregation and ensure correct assembly.
- Nucleosome formation is driven by electrostatic interactions, counterion release, and DNA bending, and does not require ATP.
- In vivo, nucleosome assembly is coupled to DNA replication and transcription, with CAF-1 mediating replication-coupled assembly and FACT and HIRA mediating transcription-coupled assembly.
- Histone modifications and variants modulate nucleosome stability and function but are not required for the basic assembly process.
- Nucleosome formation is distinct from chromatin remodeling, which is an ATP-dependent process that moves or ejects nucleosomes.

## Further Reading

- Pennings S, Allan J, Davey CS. *DNA methylation, nucleosome formation and positioning*. Briefings in functional genomics & proteomics. 2005. [PubMed 15814025](https://doi.org/10.1093/bfgp/3.4.351)
- Tolkunov D, Morozov AV. *Genomic studies and computational predictions of nucleosome positions and formation energies*. Advances in protein chemistry and structural biology. 2010. [PubMed 20621280](https://doi.org/10.1016/S1876-1623(10)79001-5)
- Mahloogi H, Behe MJ. *Oligoadenosine tracts favor nucleosome formation*. Biochemical and biophysical research communications. 1997. [PubMed 9207216](https://doi.org/10.1006/bbrc.1997.6858)
- Katsumata K et al. *Sequence-dependent nucleosome formation in trinucleotide repeats evaluated by in vivo chemical mapping*. Biochemical and biophysical research communications. 2021. [PubMed 33839413](https://doi.org/10.1016/j.bbrc.2021.03.155)
- Hirai S et al. *Unusual nucleosome formation and transcriptome influence by the histone H3mm18 variant*. [Nucleic acids research](/blog/news/nucleic-acids-research). 2022. [PubMed 34929737](https://doi.org/10.1093/nar/gkab1137)
- Guan R et al. *Structural and dynamic mechanisms of CBF3-guided centromeric nucleosome formation*. Nature communications. 2021. [PubMed 33741944](https://doi.org/10.1038/s41467-021-21985-9)

## Related Topics

- [Nucleosome Structure](/knowledge/molecular-biology/nucleosome-structure)
- [Nucleosome Model](/knowledge/molecular-biology/nucleosome-model)
- [Nucleosome Definition](/knowledge/molecular-biology/nucleosome-definition)
- [Histone Nucleosome](/knowledge/molecular-biology/histone-nucleosome)
- [Nucleosome Chromatin](/knowledge/molecular-biology/nucleosome-chromatin)

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* [Nucleotide Formation: Biosynthesis and Assembly of DNA/RNA Building Blocks](/knowledge/molecular-biology/nucleotide-formation)