scholarly journals Histone tails cooperate to control the breathing of genomic nucleosomes

2020 ◽  
Author(s):  
Jan Huertas ◽  
Hans R Schöler ◽  
Vlad Cojocaru
Keyword(s):  
Epigenetic Regulation ◽  
Genomic Dna ◽  
Histone H3 ◽  
Molecular Simulations ◽  
Dna Interaction ◽  
Structural Transitions ◽  
Histone Tail ◽  
Chemical Modifications ◽  
Histone Tails ◽  
Chromatin Dynamics

Genomic DNA is packaged in chromatin, a dynamic fiber variable in size and compaction. In chromatin, repeating nucleosome units wrap 146 DNA basepairs around histone proteins. Genetic and epigenetic regulation of genes relies on structural transitions in chromatin which are driven by intra- and internucleosome dynamics and modulated by chemical modifications of the unstructured terminal tails of histones. Here we demonstrate how the interplay between histone H3 and H2A tails control ample nucleosome breathing motions. We monitored large openings of two genomic nucleosomes, and only moderate breathing of an engineered nucleosome in atomistic molecular simulations amounting to 18μs. Transitions between open and closed nucleosome conformations were driven by the displacement and changes in compaction of the two histone tails. These motions involved changes in the DNA interaction profiles of clusters of epigenetic regulatory aminoacids in the tails. Histone tail modulated nucleosome breathing is a key mechanism of chromatin dynamics.

scholarly journals Histone tails cooperate to control the breathing of genomic nucleosomes

2021 ◽  
Vol 17 (6) ◽  
pp. e1009013
Author(s):  
Jan Huertas ◽  
Hans Robert Schöler ◽  
Vlad Cojocaru
Keyword(s):  
Epigenetic Regulation ◽  
Genomic Dna ◽  
Histone H3 ◽  
Molecular Simulations ◽  
Dna Interaction ◽  
Histone Tail ◽  
Chemical Modifications ◽  
Histone Tails ◽  
Chromatin Dynamics ◽  
Nucleosome Dynamics

Genomic DNA is packaged in chromatin, a dynamic fiber variable in size and compaction. In chromatin, repeating nucleosome units wrap 145–147 DNA basepairs around histone proteins. Genetic and epigenetic regulation of genes relies on structural transitions in chromatin which are driven by intra- and inter-nucleosome dynamics and modulated by chemical modifications of the unstructured terminal tails of histones. Here we demonstrate how the interplay between histone H3 and H2A tails control ample nucleosome breathing motions. We monitored large openings of two genomic nucleosomes, and only moderate breathing of an engineered nucleosome in atomistic molecular simulations amounting to 24 μs. Transitions between open and closed nucleosome conformations were mediated by the displacement and changes in compaction of the two histone tails. These motions involved changes in the DNA interaction profiles of clusters of epigenetic regulatory aminoacids in the tails. Removing the histone tails resulted in a large increase of the amplitude of nucleosome breathing but did not change the sequence dependent pattern of the motions. Histone tail modulated nucleosome breathing is a key mechanism of chromatin dynamics with important implications for epigenetic regulation.

scholarly journals Reconstitution of recombinant chromatin establishes a requirement for histone-tail modifications during chromatin assembly and transcription

2001 ◽  
Vol 15 (21) ◽  
pp. 2837-2851
Author(s):  
Alejandra Loyola ◽  
Gary LeRoy ◽  
Yuh-Hwa Wang ◽  
Danny Reinberg
Keyword(s):  
Rna Polymerase Ii ◽  
Histone H3 ◽  
Dependent Manner ◽  
Histone Tail ◽  
Histone Tails ◽  
Transcription System ◽  
Nuclear Extracts ◽  
Chromatin Acetylation ◽  
Rna Polymerase Ii Transcription ◽  
Nucleosome Arrays

The human ISWI-containing factor RSF (remodeling andspacing factor) was found to mediate nucleosome deposition and, in the presence of ATP, generate regularly spaced nucleosome arrays. Using this system, recombinant chromatin was reconstituted with bacterially produced histones. Acetylation of the histone tails was found to play an important role in establishing regularly spaced nucleosome arrays. Recombinant chromatin lacking histone acetylation was impaired in directing transcription. Histone-tail modifications were found to regulate transcription from the recombinant chromatin. Acetylation of the histone tails by p300 was found to increase transcription. Methylation of the histone H3 tail by Suv39H1 was found to repress transcription in an HP1-dependent manner. The effects of histone-tail modifications were observed in nuclear extracts. A highly reconstituted RNA polymerase II transcription system was refractory to the effect imposed by acetylation and methylation.

scholarly journals Persistent Interactions of Core Histone Tails with Nucleosomal DNA following Acetylation and Transcription Factor Binding

1998 ◽  
Vol 18 (11) ◽  
pp. 6293-6304 ◽  
Author(s):  
Vesco Mutskov ◽  
Delphine Gerber ◽  
Dimitri Angelov ◽  
Juan Ausio ◽  
Jerry Workman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Biology ◽  
Binding Sites ◽  
Cross Linking ◽  
Uv Laser ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosomal Dna ◽  
Core Histones

ABSTRACT In this study, we examined the effect of acetylation of the NH2 tails of core histones on their binding to nucleosomal DNA in the absence or presence of bound transcription factors. To do this, we used a novel UV laser-induced protein-DNA cross-linking technique, combined with immunochemical and molecular biology approaches. Nucleosomes containing one or five GAL4 binding sites were reconstituted with hypoacetylated or hyperacetylated core histones. Within these reconstituted particles, UV laser-induced histone-DNA cross-linking was found to occur only via the nonstructured histone tails and thus presented a unique tool for studying histone tail interactions with nucleosomal DNA. Importantly, these studies demonstrated that the NH2 tails were not released from nucleosomal DNA upon histone acetylation, although some weakening of their interactions was observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH dimers to nucleosomes occupying the central 90 bp occurred without displacement of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of each histone tail with nucleosomal DNA to different degrees. However, in all cases, greater than 50% of the interactions between the histone tails and DNA was retained upon GAL4-AH binding, even if the tails were highly acetylated. These data illustrate an interaction of acetylated or nonacetylated histone tails with DNA that persists in the presence of simultaneously bound transcription factors.

scholarly journals Histone transfer among chaperones

2012 ◽  
Vol 40 (2) ◽  
pp. 357-363 ◽  
Author(s):  
Wallace H. Liu ◽  
Mair E.A. Churchill
Keyword(s):  
Histone H3 ◽  
Histone Chaperone ◽  
Chromatin Assembly ◽  
Histone Chaperones ◽  
Nucleosome Assembly ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Nucleosomal Dna ◽  
Chaperone Interactions ◽  
Dependent Processes

The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.

scholarly journals Histone Tails and the H3 αN Helix Regulate Nucleosome Mobility and Stability

2007 ◽  
Vol 27 (11) ◽  
pp. 4037-4048 ◽  
Author(s):  
Helder Ferreira ◽  
Joanna Somers ◽  
Ryan Webster ◽  
Andrew Flaus ◽  
Tom Owen-Hughes
Keyword(s):  
Dynamic Properties ◽  
Histone H3 ◽  
Fine Tuning ◽  
Histone Tails ◽  
Histone Proteins ◽  
Regulatory Factors ◽  
Nucleosome Dynamics ◽  
Nucleosome Sliding ◽  
Eukaryotic Genomes ◽  
Dna Wrapping

ABSTRACT Nucleosomes fulfill the apparently conflicting roles of compacting DNA within eukaryotic genomes while permitting access to regulatory factors. Central to this is their ability to stably associate with DNA while retaining the ability to undergo rearrangements that increase access to the underlying DNA. Here, we have studied different aspects of nucleosome dynamics including nucleosome sliding, histone dimer exchange, and DNA wrapping within nucleosomes. We find that alterations to histone proteins, especially the histone tails and vicinity of the histone H3 αN helix, can affect these processes differently, suggesting that they are mechanistically distinct. This raises the possibility that modifications to histone proteins may provide a means of fine-tuning specific aspects of the dynamic properties of nucleosomes to the context in which they are located.

Epigenetic regulation of adipogenesis by histone-modifying enzymes

Epigenomics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 235-251
Author(s):  
Paolo E Macchia ◽  
Immacolata C Nettore ◽  
Fabiana Franchini ◽  
Laura Santana-Viera ◽  
Paola Ungaro
Keyword(s):  
Epigenetic Regulation ◽  
Transcriptional Control ◽  
Metabolic Diseases ◽  
Epigenetic Mechanisms ◽  
Differentiation Process ◽  
Histone Tails ◽  
Histone Modifying Enzymes ◽  
Epigenomic Regulation ◽  
Adipocyte Development

Many studies investigating the transcriptional control of adipogenesis have been published so far; recently the research is focusing on the role of epigenetic mechanisms in regulating the process of adipocyte development. Histone-modifying enzymes and the histone tails post-transcriptional modifications catalyzed by them, are fundamentally involved in the epigenetic regulation of adipogenesis. In our review, we will discuss recent advances in epigenomic regulation of adipogenesis with a focus on histone-modifying enzymes implicated in the various phases of adipocytes differentiation process from mesenchymal stem cells to mature adipocytes. Understanding adipogenesis, may provide new ways to treat obesity and related metabolic diseases.

313. EPIGENETIC REGULATION OF THE CRH GENE PROMOTER INVOLVES SPECIFIC CpG DE-METHYLATION

2010 ◽  
Vol 22 (9) ◽  
pp. 113
Author(s):  
X. Pan ◽  
C. Abou-Seif ◽  
M. Allars ◽  
Y. Chen ◽  
R. C. Nicholson
Keyword(s):  
Epigenetic Regulation ◽  
Genomic Dna ◽  
Methylation Status ◽  
Gene Promoter ◽  
Bewo Cell ◽  
Gestational Length ◽  
Partial Methylation ◽  
Peripheral Tissues ◽  
Cpg Sites ◽  
Bewo Cells

Corticotropin Releasing Hormone (CRH), is expressed in many regions of the central nervous system and in some peripheral tissues, and plays an important role in determining gestational length. In placenta, a cAMP regulatory site (CRE) is crucial for CRH gene regulation. The promoter of CRH gene has 9 CpG sites, which should be the targets of epigenetic regulation by DNA methylation. The BeWo cell line, derived from human gestational choriocarcinoma, has been widely used as an in vitro model for the placenta. BeWo cells only produce CRH after exposure to cAMP. The DNA methyl transferase (DNMT) inhibitor 5-aza-cytidine stimulates CRH expression 5-fold in camp treated BeWo cells, indicating the CRH promoter as a target of DNMTs. To evaluate methylation differences of the 9 CpG sites in CRH gene promoter in BeWo cells after treatment with cAMP. Genomic DNA was extracted from BeWo cells treated or not with cAMP. Sodium bisulfite conversion was used to modify the genomic DNA. PCR was used to amplify the CRH promoter region with primers that did not contain CpG sites. The PCR products were cloned and sequenced. The CpG methylation status of each sample was obtained by comparing the sequencing results with the original sequence. In non-stimulated cells (control) CpG -4 was methylated in 50% of the clones and CpG -6 was methylated in 75% of the clones, but the other 7 sites were methylated in every clone. In the cAMP treated cells however there was 100% methylation at CpG sites 6 through 9, but only partial methylation at CpG-1 and 3 (60%), CpG-4 and 5 (40%). Most interestingly, there was no methylation found at CpG-2 in any of the clones from cAMP treated cells, indicating that specific CpG de-methylation around the CRE is required for CRH gene expression.

scholarly journals Dynamics of the nucleosomal histone H3 N-terminal tail revealed by high precision single-molecule FRET

2020 ◽  
Vol 48 (3) ◽  
pp. 1551-1571 ◽  
Author(s):  
Kathrin Lehmann ◽  
Suren Felekyan ◽  
Ralf Kühnemuth ◽  
Mykola Dimura ◽  
Katalin Tóth ◽  
...  
Keyword(s):  
Single Molecule ◽  
Histone H3 ◽  
Time Range ◽  
Histone H2a ◽  
Histone Tails ◽  
Dna Accessibility ◽  
Single Molecule Fret ◽  
Multiple Interaction ◽  
Nucleosome Disassembly ◽  
Dynamic Transitions

Abstract Chromatin compaction and gene accessibility are orchestrated by assembly and disassembly of nucleosomes. Although the disassembly process was widely studied, little is known about the structure and dynamics of the disordered histone tails, which play a pivotal role for nucleosome integrity. This is a gap filling experimental FRET study from the perspective of the histone H3 N-terminal tail (H3NtT) of reconstituted mononucleosomes. By systematic variation of the labeling positions we monitored the motions of the H3NtT relative to the dyad axis and linker DNA. Single-molecule FRET unveiled that H3NtTs do not diffuse freely but follow the DNA motions with multiple interaction modes with certain permitted dynamic transitions in the μs to ms time range. We also demonstrate that the H3NtT can allosterically sense charge-modifying mutations within the histone core (helix α3 of histone H2A (R81E/R88E)) resulting in increased dynamic transitions and lower rate constants. Those results complement our earlier model on the NaCl induced nucleosome disassembly as changes in H3NtT configurations coincide with two major steps: unwrapping of one linker DNA and weakening of the internal DNA - histone interactions on the other side. This emphasizes the contribution of the H3NtT to the fine-tuned equilibrium between overall nucleosome stability and DNA accessibility.

scholarly journals Role of Histone N-Terminal Tails and Their Acetylation in Nucleosome Dynamics

2000 ◽  
Vol 20 (19) ◽  
pp. 7230-7237 ◽  
Author(s):  
Violette Morales ◽  
Hélène Richard-Foy
Keyword(s):  
Topoisomerase I ◽  
Globular Domain ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosome Dynamics ◽  
Nucleosome Structure ◽  
Left Handed ◽  
Negative Supercoiling ◽  
And Function

ABSTRACT Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)2 tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of histone tail cleavage and histone tail acetylation on the structure of the nucleoprotein particle was investigated by analyzing the DNA topoisomer equilibrium after relaxation of DNA torsional stress by topoisomerase I. Removal of the H3 and H4 N-terminal tails, as well as their acetylation, provoked a dramatic change in the linking-number difference of the (H3-H4)2 tetrameric particle, with a release of up to 70% of the negative supercoiling previously constrained by this structure. The (H3-H4)2 tetramers containing tailless or hyperacetylated histones showed a striking preference for relaxed DNA over negatively supercoiled DNA. This argues in favor of a change in tetramer structure that constrains less DNA and adopts a relaxed flat conformation instead of its left-handed conformation within the nucleosome. In contrast neither removal or hyperacetylation of H3 and H4 tails nor removal or hyperacetylation of H2A and H2B N-terminal tails affected the nucleosome structure. This indicates that the globular domain of H2A and H2B is sufficient to stabilize the tailless or the hyperacetylated (H3-H4)2tetramer in a left-handed superhelix conformation. These results suggest that the effect of histone tail acetylation that facilitates transcription may be mediated via transient formation of an (H3-H4)2 tetrameric particle that could adopt an open structure only when H3 and/or H4 tails are hyperacetylated.

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