Featuring the nucleosome surface as a therapeutic target

Silva, Isabel Torres Gomes da; Oliveira, Paulo Sérgio Lopes de; Santos, Guilherme

doi:10.1016/j.tips.2015.02.010

Cited by 11 publications

(13 citation statements)

References 40 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future work in this area will undoubtedly reveal the extent of arginine anchor usage and uncover new paradigms for nucleosome recognition. Ultimately, the combined structural knowledge may inform the design of small molecule or peptidomimetic modulators of chromatin structure and function [56]. …”

Section: Future Directionsmentioning

confidence: 99%

Recognition of the nucleosome by chromatin factors and enzymes

McGinty

Tan

2016

Current Opinion in Structural Biology

122

View full text Add to dashboard Cite

Dynamic expression of the genome requires coordinated binding of chromatin factors and enzymes that carry out genome-templated processes. Until recently, the molecular mechanisms governing how these factors and enzymes recognize and act on the fundamental unit of chromatin, the nucleosome core particle, have remained a mystery. A small, yet growing set of structures of the nucleosome in complex with chromatin factors and enzymes highlights the importance of multivalency in defining nucleosome binding and specificity. Many such interactions include an arginine anchor motif, which targets a unique acidic patch on the nucleosome surface. These emerging paradigms for chromatin recognition will be discussed, focusing on several recent structural breakthroughs.

show abstract

Section: Future Directionsmentioning

confidence: 99%

Recognition of the nucleosome by chromatin factors and enzymes

McGinty

Tan

2016

Current Opinion in Structural Biology

122

View full text Add to dashboard Cite

show abstract

“…The docking domain (DD) and H2B loop 1 (L1) and helix 1 (α-1). Highlighted are amino acids of the acidic patch (E91′ and E92′ from H2A′), of the H4/H4′ tail (H18, R19, K20, L22, R23), and amino acids F78, E133′ from H3 and R96, K105 from H2B, which were previously reported to bind NBPs (5). …”

Section: Resultsmentioning

confidence: 99%

“…Although chromatin structural and functional states are largely defined by nucleosome binding proteins (NBPs) and the state of the histone H4 tail (5), the nuclear environment comprises several small molecules that may directly bind to chromatin [e.g., magnesium (6) and lipids (7)]. Conceivably, all these substances may have a considerable impact on chromatin architecture.…”

mentioning

confidence: 99%

Biophysical studies of cholesterol effects on chromatin

Silva

Fernandes

Souza

et al. 2017

Journal of Lipid Research

View full text Add to dashboard Cite

Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol’s action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to the nucleosome. Our findings support that cholesterol assists 10 and 30 nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.

show abstract

“…Investigations of other structural domains on the nucleosomal surface have been performed, leading to D r a f t novel findings that include the presence of a structured and negatively charged region adjacent to the H2A-H2B acidic patch. This acidic pocket is composed of three residues within H3 and one residue from H4 residues (da Silva et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the acidic patch is implicated as a crucial interaction platform for many nucleosome-protein D r a f t complexes, some of which have been structurally demonstrated. For instance, the first complex structure of a nucleosome-peptide that was resolved and biochemically described was the viral peptide LANA from KSHV bound with the nucleosome (Barbera et al 2006;da Silva et al 2015;Kalashnikova et al 2013).…”

Section: Nucleosome Acidic Patch Interacting Factorsmentioning

confidence: 99%

The nucleosome: orchestrating DNA damage signaling and repair within chromatin

Agarwal

Miller

2016

Biochem. Cell Biol.

View full text Add to dashboard Cite

DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

show abstract

Featuring the nucleosome surface as a therapeutic target

Cited by 11 publications

References 40 publications

Recognition of the nucleosome by chromatin factors and enzymes

Recognition of the nucleosome by chromatin factors and enzymes

Biophysical studies of cholesterol effects on chromatin

The nucleosome: orchestrating DNA damage signaling and repair within chromatin

Contact Info

Product

Resources

About