scholarly journals Lysine succinylation on non-histone chromosomal protein HMG-17 (HMGN2) regulates nucleosomal DNA accessibility by disrupting HMGN2-nucleosome association

2021 ◽  
Author(s):  
Yihang Jing ◽  
Gaofei Tian ◽  
Xiaoyu Qin ◽  
Zheng Liu ◽  
Xiang David Li
Keyword(s):  
Posttranslational Modification ◽  
Chromosomal Protein ◽  
Histone Proteins ◽  
Dna Accessibility ◽  
Nucleosome Dynamics ◽  
Lysine Succinylation ◽  
Nucleosomal Dna ◽  
Chromatin Proteins ◽  
Dna Unwrapping

Lysine succinylation (Ksucc) is a novel posttranslational modification that frequently occurs on chromatin proteins including histones and non-histone proteins. Histone Ksucc affects nucleosome dynamics by increasing DNA unwrapping rate and...

scholarly journals DNA methylation cues in nucleosome geometry, stability, and unwrapping

2021 ◽  
Author(s):  
Shuxiang Li ◽  
Yunhui Peng ◽  
David Landsman ◽  
Anna Panchenko
Keyword(s):  
Conformational Changes ◽  
Cytosine Methylation ◽  
Epigenetic Mark ◽  
Nucleosome Assembly ◽  
Functional Studies ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations ◽  
Eukaryotic Organisms

Cytosine methylation at the 5-carbon position is an essential DNA epigenetic mark in many eukaryotic organisms. Although countless structural and functional studies of cytosine methylation have been reported in both prokaryotes and eukaryotes, our understanding of how it influences the nucleosome assembly, structure, and dynamics remains obscure. Here we investigated the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability. By applying long molecular dynamics simulations (five microsecond long trajectories, 60 microseconds in total), we generated extensive atomic level conformational full nucleosome ensembles. Our results revealed that methylation induces pronounced changes in geometry for both linker and nucleosomal DNA, leading to a more curved, under-twisted DNA, shifting the population equilibrium of sugar-phosphate backbone geometry. These conformational changes are associated with a considerable enhancement of interactions between methylated DNA and the histone octamer, doubling the number of contacts at some key arginines. H2A and H3 tails play important roles in these interactions, especially for DNA methylated nucleosomes. This, in turn, prevents a spontaneous DNA unwrapping of 3-4 helical turns for the methylated nucleosome with truncated histone tails, otherwise observed in the unmethylated system on several microsecond time scale.

scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasiia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosome Core Particles ◽  
Nucleosomal Dna ◽  
Dna Base ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ∼147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucleosomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.

scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes: insights from multi-microsecond molecular dynamics simulations

2021 ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ~147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucle-osomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.We developed a web site for an interactive preview of molecular dynamics trajectories at https://intbio.github.io/Armeev_et_al_2021.

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.

Some effects of treatment of hen erythrocytes in vitro with N-methyl-N-nitrosourea

1981 ◽  
Vol 51 (1) ◽  
pp. 153-162
Author(s):  
T.H. Ward ◽  
R.F. Itzhaki
Keyword(s):  
Metabolic Activity ◽  
Cell Types ◽  
Condensed State ◽  
Methylation Site ◽  
Histone Proteins ◽  
Chromatin Proteins

Studies have been made of the effect of N-methyl-N-nitrosourea on hen erythrocytes in vitro. These were done to find whether the highly condensed state of the chromatin and the very low metabolic activity of these cells would affect the extent of methylation of the DNA and chromatin proteins and the persistence of any methylation sites in these macromolecules with time after treatment. Also, the effect of methylnitrosourea on incorporation of [3H] uridine into RNA has been examined. It has been found that the DNA, histones and non-histone proteins are methylated. The main methylation site in DNA is 7-methylguanine and its level is higher than that found by others in the DNA of other cell types after treatment with methylnitrosourea; however, methylation of the two types of protein (especially the histones) is relatively very low. The level of methylation decreases in the DNA and the chromatin proteins with time after treatment. The amount of [3H] uridine in RNA was found to decrease after the treatment.

Recent advances in histone glycation: emerging role in diabetes and cancer

Glycobiology ◽  
2021 ◽  
Author(s):  
Abdul Rouf Mir ◽  
Safia Habib ◽  
Moin Uddin
Keyword(s):  
Structural Integrity ◽  
Cell Function ◽  
Nuclear Proteins ◽  
Chromatin Interaction ◽  
Epigenetic Landscape ◽  
Histone Proteins ◽  
Nucleosome Dynamics ◽  
Circulating Antibodies ◽  
And Function ◽  
By Products

Abstract Ever increasing information on genome and proteome has offered fascinating details and new opportunities to understand the molecular biology. It is now known that histone proteins surrounding the DNA play a crucial role in the chromatin structure and function. Histones undergo a plethora of posttranslational enzymatic modifications that influence nucleosome dynamics and affect DNA activity. Earlier research offered insights into the enzymatic modifications of histones; however, attention has been diverted to histone modifications induced by by-products of metabolism without enzymatic engagement in the last decade. Nonenzymatic modifications of histones are believed to be crucial for epigenetic landscape, cellular fate and for role in human diseases. Glycation of histone proteins constitutes the major non enzymatic modifications of nuclear proteins that have implications in diabetes and cancer. It has emerged that glycation damages nuclear proteins, modifies amino acids of histones at crucial locations, generates adducts affecting histone chromatin interaction, develops neo-epitopes inducing specific immune response and impacts cell function. Presence of circulating antibodies against glycated histone proteins in diabetes and cancer has shown immunological implications with diagnostic relevance. These crucial details make histone glycation an attractive focus for investigators. This review article, therefore, makes an attempt to exclusively summarize the recent researches in histone glycation, its impact on structural integrity of chromatin and elaborates on their role in diabetes and cancer. The work offers insights for future scientists who investigate the link between metabolism, biomolecular structures, glycobiology, histone–DNA interactions in relation to diseases in humans.

scholarly journals Nonhistone protein antigen profiles of five leukemic cell lines reflect the extent of myeloid differentiation

Blood ◽  
1984 ◽  
Vol 63 (3) ◽  
pp. 701-710 ◽  
Author(s):  
A Goldberger ◽  
G Brewer ◽  
LS Hnilica ◽  
RC Briggs
Keyword(s):  
Cell Lines ◽  
Myeloid Cell ◽  
Leukemic Cell ◽  
Nuclear Extract ◽  
Myeloid Differentiation ◽  
Chromosomal Protein ◽  
Protein Antigens ◽  
Nonhistone Protein ◽  
Leukemic Cell Lines ◽  
Chromatin Proteins

Abstract The human leukemic cell lines, K562, KG-1, and HL-60, and the blast subclones, KG-1a and HL-60 blast, were utilized to relate differences in nonhistone protein antigens to stages of myeloid cell differentiation. Chromatin proteins were separated on SDS- polyacrylamide gels, transferred electrophoretically to nitrocellulose sheets, and visualized by the peroxidase-antiperoxidase method of Sternberger. Screening with antisera raised against total and dehistonized chromatin and a nuclear extract from these cells revealed quantitative as well as qualitative differences between the cell lines. A decrease in antigen content seemed to parallel progressive stages of myeloid cell development. The results indicate that a number of chromosomal protein antigens are lost or modified during differentiation. An antigen(s) of approximately 55,000 molecular weight was found in HL-60 chromatin, but was not present in its less differentiated subclone or in the other lines representative of earlier stage cells. Upon the induction of HL-60 cells to mature to end stages with 4 microM retinoic acid, a significant increase in the mol wt 55,000 activity was seen. This antigen was detected only with antisera against HL-60 total chromatin and granulocyte nuclei, and it was found only in normal mature granulocytes and in the later stage cells of the HL-60 culture. Thus, the antigen appears to be associated with a differentiated myeloid function.

scholarly journals Effect of erythropoietin on chromosomal protein synthesis

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 581-592 ◽  
Author(s):  
JL Spivak
Keyword(s):  
Isotope Labeling ◽  
Specific Activity ◽  
Splenic Tissue ◽  
Chromosomal Protein ◽  
Histone Proteins ◽  
Total Histone ◽  
Chromosomal Proteins ◽  
Nonhistone Protein ◽  
The Individual ◽  
Double Isotope

Abstract The spleen of the exhypoxic polycythemic mouse was employed to study the effect of erythropoietin on the synthesis of chromosomal proteins. At 1, 3, 18, 36, 45, and 72 hr after injection of erythropoietin, spleens were removed, minced, and incubated with 3H-arginine for 1 hr. Chromatin was isolated from the labeled splenic tissue and separated into histone and nonhistone protein (NHP) fractions. An increase in the incorporation of 3H-arginine into NHP occurred within 3 hr and into histones by 18 hr. Incorporation of 3H-arginine into both histones and NHP was maximal by 45 hr and had declined by 72 hr. Total histone specific activity increased fivefold while NHP specific activity increased twofold. Histones and NHP were fractionated on polyacrylamide gels and a double isotope labeling proceudre was used to study the synthesis of the individual histone proteins and NHP. Following administration of erythropoietin, there was a coordinate increase in the specific activity of all five major histone proteins and most of the NHP. The earliest change in specific activity of both histones and NHP occurred prior to the appearance of morphologically identifiable erythroblasts in the spleen.

scholarly journals Genomic methods in profiling DNA accessibility and factor localization

2019 ◽  
Vol 28 (1) ◽  
pp. 69-85 ◽  
Author(s):  
David C. Klein ◽  
Sarah J. Hainer
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Regulatory Regions ◽  
Histone Proteins ◽  
Putative Gene ◽  
Factor Binding ◽  
Advantages And Disadvantages ◽  
Dna Accessibility

AbstractRecent advancements in next-generation sequencing technologies and accompanying reductions in cost have led to an explosion of techniques to examine DNA accessibility and protein localization on chromatin genome-wide. Generally, accessible regions of chromatin are permissive for factor binding and are therefore hotspots for regulation of gene expression; conversely, genomic regions that are highly occupied by histone proteins are not permissive for factor binding and are less likely to be active regulatory regions. Identifying regions of differential accessibility can be useful to uncover putative gene regulatory regions, such as enhancers, promoters, and insulators. In addition, DNA-binding proteins, such as transcription factors that preferentially bind certain DNA sequences and histone proteins that form the core of the nucleosome, play essential roles in all DNA-templated processes. Determining the genomic localization of chromatin-bound proteins is therefore essential in determining functional roles, sequence motifs important for factor binding, and regulatory networks controlling gene expression. In this review, we discuss techniques for determining DNA accessibility and nucleosome positioning (DNase-seq, FAIRE-seq, MNase-seq, and ATAC-seq) and techniques for detecting and functionally characterizing chromatin-bound proteins (ChIP-seq, DamID, and CUT&RUN). These methods have been optimized to varying degrees of resolution, specificity, and ease of use. Here, we outline some advantages and disadvantages of these techniques, their general protocols, and a brief discussion of their development. Together, these complimentary approaches have provided an unparalleled view of chromatin architecture and functional gene regulation.

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