scholarly journals Ion counting demonstrates a high electrostatic field generated by the nucleosome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Magdalena Gebala ◽  
Stephanie L Johnson ◽  
Geeta J Narlikar ◽  
Dan Herschlag
Keyword(s):  
Electrostatic Field ◽  
Nuclear Dna ◽  
Chromatin Organization ◽  
Computational Studies ◽  
Compaction Process ◽  
Histone Protein ◽  
Dna Compaction ◽  
Nucleosome Formation ◽  
And Function ◽  
Positively Charged

In eukaryotes, a first step towards the nuclear DNA compaction process is the formation of a nucleosome, which is comprised of negatively charged DNA wrapped around a positively charged histone protein octamer. Often, it is assumed that the complexation of the DNA into the nucleosome completely attenuates the DNA charge and hence the electrostatic field generated by the molecule. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing views of nucleosome electrostatics have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.

scholarly journals Ion counting demonstrates a high electrostatic potential of the nucleosome

2019 ◽  
Author(s):  
Magdalena Gebala ◽  
Stephanie Johnson ◽  
Geeta Narlikar ◽  
Daniel Herschlag
Keyword(s):  
Electrostatic Field ◽  
Dna Binding Proteins ◽  
Electrostatic Repulsion ◽  
Computational Studies ◽  
Histone Protein ◽  
Dna Compaction ◽  
Histone Octamer ◽  
Nucleosome Formation ◽  
And Function ◽  
Positively Charged

AbstractThe fundamental unit of chromatin is the nucleosome, which comprises of DNA wrapped around a histone protein octamer. The association of positively charged histone proteins with negatively charged DNA is intuitively thought to attenuate the electrostatic repulsion of DNA, resulting in a weakly charged nucleosome complex. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing models have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Further, our results show that the wrapping of DNA around a histone octamer increases the propensity of the DNA to make interactions with multivalent cations like Mg2+. These findings indicate that presentation of DNA on a nucleosome may more strongly attract positively-charged DNA binding proteins. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.

scholarly journals DNA sliding and loop formation by E. coli SMC complex: MukBEF

2021 ◽  
Author(s):  
man zhou
Keyword(s):  
Single Molecule ◽  
Atp Hydrolysis ◽  
Dna Interaction ◽  
Loop Formation ◽  
Unknown Mechanism ◽  
E Coli ◽  
Dna Compaction ◽  
And Function ◽  
Structural Maintenance Of Chromosomes

SMC (structural maintenance of chromosomes) complexes share conserved architectures and function in chromosome maintenance via an unknown mechanism. Here we have used single-molecule techniques to study MukBEF, the SMC complex in Escherichia coli. Real-time movies show MukB alone can compact DNA and ATP inhibits DNA compaction by MukB. We observed that DNA unidirectionally slides through MukB, potentially by a ratchet mechanism, and the sliding speed depends on the elastic energy stored in the DNA. MukE, MukF and ATP binding stabilize MukB and DNA interaction, and ATP hydrolysis regulates the loading/unloading of MukBEF from DNA. Our data suggests a new model for how MukBEF organizes the bacterial chromosome in vivo; and this model will be relevant for other SMC proteins.

Oxidative stress-induced cell death of human oral neutrophils

2003 ◽  
Vol 284 (4) ◽  
pp. C1048-C1053 ◽  
Author(s):  
Eisuke F. Sato ◽  
Masahiro Higashino ◽  
Kazuo Ikeda ◽  
Ryotaro Wake ◽  
Mitsuyoshi Matsuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Caspase 3 ◽  
Nuclear Dna ◽  
Kinase Inhibitor ◽  
Tissue Injury ◽  
Morphological Changes ◽  
Limited Information ◽  
And Function

Polymorphonuclear leukocytes (PMN) play crucial roles in protecting hosts against invading microbes and in the pathogenesis of inflammatory tissue injury. Although PMN migrate into mucosal layers of digestive and respiratory tracts, only limited information is available of their fate and function in situ. We previously reported that, unlike circulating PMN (CPMN), PMN in the oral cavity spontaneously generate superoxide radical and nitric oxide (NO) in the absence of any stimuli. When cultured for 12 h under physiological conditions, oral PMN (OPMN) showed morphological changes that are characteristic of those of apoptosis. Upon agarose gel electrophoresis, nuclear DNA samples isolated from OPMN revealed ladder-like profiles characteristic of nucleosomal fragmentation.l-cysteine, reduced glutathione (GSH), and herbimycin A, a protein tyrosine kinase inhibitor, suppressed the activation of caspase-3 and apoptosis of OPMN. Neither thiourea, superoxide dismutase (SOD), nor catalase inhibited the activation of caspase-3 and apoptosis. Moreover, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibitor for caspase-3, inhibited the fragmentation of DNA. These results suggested that oxidative stress and/or tyrosine-kinase-dependent pathway(s) activated caspase-3 in OPMN, thereby inducing their apoptosis.

scholarly journals Renal ischemia alters expression of mitochondria-related genes and impairs mitochondrial structure and function in swine scattered tubular-like cells

2020 ◽  
Vol 319 (1) ◽  
pp. F19-F28 ◽  
Author(s):  
Rahele A. Farahani ◽  
Xiang-Yang Zhu ◽  
Hui Tang ◽  
Kyra L. Jordan ◽  
Lilach O. Lerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Structural Damage ◽  
Nuclear Dna ◽  
Mitochondrial Genes ◽  
Structure And Function ◽  
Mitochondrial Damage ◽  
Renal Ischemia ◽  
Gene Gain ◽  
Mitochondrial Structure ◽  
And Function

Scattered tubular-like cells (STCs) are dedifferentiated surviving tubular epithelial cells that repair neighboring injured cells. Experimental renal artery stenosis (RAS) impairs STC reparative potency by inducing mitochondrial injury, but the exact mechanisms of mitochondrial damage remain unknown. We hypothesized that RAS alters expression of mitochondria-related genes, contributing to mitochondrial structural damage and dysfunction in swine STCs. CD24+/CD133+ STCs were isolated from pig kidneys after 10 wk of RAS or sham ( n = 3 each). mRNA sequencing was performed, and nuclear DNA (nDNA)-encoded mitochondrial genes and mitochondrial DNA (mtDNA)-encoded genes were identified. Mitochondrial structure, ATP generation, biogenesis, and expression of mitochondria-associated microRNAs were also assessed. There were 96 nDNA-encoded mitochondrial genes upregulated and 12 mtDNA-encoded genes downregulated in RAS-STCs versus normal STCs. Functional analysis revealed that nDNA-encoded and mtDNA-encoded differentially expressed genes were primarily implicated in mitochondrial respiration and ATP synthesis. Mitochondria from RAS STCs were swollen and showed cristae remodeling and loss and decreased ATP production. Immunoreactivity of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and expression of the mitochondria-associated microRNAs miR-15a, miR-181a, miR-196a, and miR-296-3p, which target several mtDNA genes, were higher in RAS-STCs compared with normal STCs, suggesting a potential modulation of mitochondria-related gene expression. These results demonstrate that RAS induces an imbalance in mtDNA- and nDNA-mitochondrial gene expression, impairing mitochondrial structure and function in swine STCs. These observations support development of gene gain- and loss-of-function strategies to ameliorate mitochondrial damage and preserve the reparative potency of STCs in patients with renal ischemia.

scholarly journals The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

2018 ◽  
Vol 20 (1) ◽  
pp. 102 ◽  
Author(s):  
Justine Habibian ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Protein Phosphorylation ◽  
Cross Talk ◽  
Electrostatic Interactions ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Protein Activity ◽  
Histone Protein ◽  
Signal Transduction Protein ◽  
And Function

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

scholarly journals Structure of the H1 C-terminal domain and function in chromatin condensationThis paper is one of a selection of papers published in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Tamara L. Caterino ◽  
Jeffrey J. Hayes
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
Special Issue ◽  
Direct Role ◽  
Linker Histones ◽  
Terminal Domain ◽  
Chromatin Folding ◽  
And Function ◽  
Positively Charged ◽  
Selection Of

Linker histones are multifunctional proteins that are involved in a myriad of processes ranging from stabilizing the folding and condensation of chromatin to playing a direct role in regulating gene expression. However, how this class of enigmatic proteins binds in chromatin and accomplishes these functions remains unclear. Here we review data regarding the H1 structure and function in chromatin, with special emphasis on the C-terminal domain (CTD), which typically encompasses approximately half of the mass of the linker histone and includes a large excess of positively charged residues. Owing to its amino acid composition, the CTD was previously proposed to function in chromatin as an unstructured polycation. However, structural studies have shown that the CTD adopts detectable secondary structure when interacting with DNA and macromolecular crowding agents. We describe classic and recent experiments defining the function of this domain in chromatin folding and emerging data indicating that the function of this protein may be linked to intrinsic disorder.

Functions of the nuclear envelope and lamina in development and disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1329-1334 ◽  
Author(s):  
Tatiana V. Cohen ◽  
Lidia Hernandez ◽  
Colin L. Stewart
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Envelope ◽  
Chromatin Organization ◽  
Signalling Pathways ◽  
Mechanical Integrity ◽  
Inherited Diseases ◽  
And Function

Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular ‘hub’ in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton.

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