scholarly journals Histone chaperones exhibit conserved functionality in nucleosome remodeling

2022 ◽  
Author(s):  
Pedro Buzon ◽  
Alejandro Velazquez-Cruz ◽  
Katiuska Gonzalez-Arzola ◽  
Antonio Diaz-Quintana ◽  
Irene Diaz-Moreno ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Level ◽  
Eukaryotic Cell ◽  
Histone Chaperone ◽  
Histone Chaperones ◽  
Dynamic Nature ◽  
Nucleosome Remodeling ◽  
Molecular Action ◽  
Core Histones

Chromatin homeostasis mediates some of the most fundamental processes in the eukaryotic cell. In this regard, histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. However, the dynamic nature of these processes has severely impeded their characterization at the molecular level. Here we apply single-molecule probing by fluorescence optical tweezers to follow histone chaperone dynamics in real-time. The molecular action of SET/template-activating factor-Iβ and nucleophosmin 1, representing the two most common histone chaperone folds, were examined using both nucleosomes and isolated core histones. We show that these chaperones present binding specificity for partially dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, we reveal that cytochrome c inhibition of histone chaperones is coupled to chaperone accumulation on DNA-bound histones. Our single-molecule approach shows that despite the drastically different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

H3–H4 Histone Chaperone Pathways

2018 ◽  
Vol 52 (1) ◽  
pp. 109-130 ◽  
Author(s):  
Prerna Grover ◽  
Jonathon S. Asa ◽  
Eric I. Campos
Keyword(s):  
Posttranslational Modifications ◽  
Nuclear Import ◽  
Genetic Material ◽  
Histone Variants ◽  
Chromatin Accessibility ◽  
Histone Chaperone ◽  
Structural Level ◽  
Histone Chaperones ◽  
Dynamic Nature ◽  
Histone Deposition

Nucleosomes compact and organize genetic material on a structural level. However, they also alter local chromatin accessibility through changes in their position, through the incorporation of histone variants, and through a vast array of histone posttranslational modifications. The dynamic nature of chromatin requires histone chaperones to process, deposit, and evict histones in different tissues and at different times in the cell cycle. This review focuses on the molecular details of canonical and variant H3–H4 histone chaperone pathways that lead to histone deposition on DNA as they are currently understood. Emphasis is placed on the most established pathways beginning with the folding, posttranslational modification, and nuclear import of newly synthesized H3–H4 histones. Next, we review the deposition of replication-coupled H3.1–H4 in S-phase and replication-independent H3.3–H4 via alternative histone chaperone pathways. Highly specialized histone chaperones overseeing the deposition of histone variants are also briefly discussed.

scholarly journals Promoter Region-Specific Histone Incorporation by the Novel Histone Chaperone ANP32B and DNA-Binding Factor KLF5

2007 ◽  
Vol 28 (3) ◽  
pp. 1171-1181 ◽  
Author(s):  
Yoshiko Munemasa ◽  
Toru Suzuki ◽  
Kenichi Aizawa ◽  
Saku Miyamoto ◽  
Yasushi Imai ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Histone Acetylation ◽  
Promoter Region ◽  
Histone Chaperone ◽  
Histone Chaperones ◽  
The Novel ◽  
Functional Interaction ◽  
Nucleosome Remodeling ◽  
Specific Regulation

ABSTRACT Regulation of chromatin in eukaryotic transcription requires histone-modifying enzymes, nucleosome remodeling complexes, and histone chaperones. Specific regulation of histone incorporation/eviction by histone chaperones on the promoter (e.g., region specific) is still poorly understood. In the present study, we show that direct and functional interaction of histone chaperone and DNA-binding transcription factor leads to promoter region-specific histone incorporation and inhibition of histone acetylation. We report here that the DNA-binding transcription factor Krüppel-like factor 5 (KLF5) interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene. We further show that recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. Extracellular stimulus (e.g., phorbol ester) regulates this mechanism in the cell. Collectively, we have identified a novel histone chaperone, ANP32B, and through analysis of the actions of this factor show a new mechanism of promoter region-specific transcriptional regulation at the chromatin level as mediated by the functional interaction between histone chaperone and DNA-binding transcription factor.

scholarly journals Human Histone Chaperone Nucleophosmin Enhances Acetylation-Dependent Chromatin Transcription

2005 ◽  
Vol 25 (17) ◽  
pp. 7534-7545 ◽  
Author(s):  
V. Swaminathan ◽  
A. Hari Kishore ◽  
K. K. Febitha ◽  
Tapas K. Kundu
Keyword(s):  
Transcriptional Activation ◽  
Histone Chaperone ◽  
Dependent Manner ◽  
Histone Chaperones ◽  
Cellular Processes ◽  
The Core ◽  
Core Histones ◽  
Nucleosomal Structure

ABSTRACT Histone chaperones are a group of proteins that aid in the dynamic chromatin organization during different cellular processes. Here, we report that the human histone chaperone nucleophosmin interacts with the core histones H3, H2B, and H4 but that this histone interaction is not sufficient to confer the chaperone activity. Significantly, nucleophosmin enhances the acetylation-dependent chromatin transcription and it becomes acetylated both in vitro and in vivo. Acetylation of nucleophosmin and the core histones was found to be essential for the enhancement of chromatin transcription. The acetylated NPM1 not only shows an increased affinity toward acetylated histones but also shows enhanced histone transfer ability. Presumably, nucleophosmin disrupts the nucleosomal structure in an acetylation-dependent manner, resulting in the transcriptional activation. These results establish nucleophosmin (NPM1) as a human histone chaperone that becomes acetylated, resulting in the enhancement of chromatin transcription.

scholarly journals The histone chaperoning pathway: from ribosome to nucleosome

2019 ◽  
Vol 63 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Alonso J. Pardal ◽  
Filipe Fernandes-Duarte ◽  
Andrew J. Bowman
Keyword(s):  
Supply And Demand ◽  
Histone Chaperone ◽  
Histone Chaperones ◽  
Post Translational Modifications ◽  
Core Histones ◽  
Eukaryotic Dna ◽  
Chaperone Interactions ◽  
Almost All ◽  
Chromatin Biology ◽  
Cellular Components

AbstractNucleosomes represent the fundamental repeating unit of eukaryotic DNA, and comprise eight core histones around which DNA is wrapped in nearly two superhelical turns. Histones do not have the intrinsic ability to form nucleosomes; rather, they require an extensive repertoire of interacting proteins collectively known as ‘histone chaperones’. At a fundamental level, it is believed that histone chaperones guide the assembly of nucleosomes through preventing non-productive charge-based aggregates between the basic histones and acidic cellular components. At a broader level, histone chaperones influence almost all aspects of chromatin biology, regulating histone supply and demand, governing histone variant deposition, maintaining functional chromatin domains and being co-factors for histone post-translational modifications, to name a few. In this essay we review recent structural insights into histone-chaperone interactions, explore evidence for the existence of a histone chaperoning ‘pathway’ and reconcile how such histone-chaperone interactions may function thermodynamically to assemble nucleosomes and maintain chromatin homeostasis.

scholarly journals Optical tweezers in single-molecule biophysics

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Carlos J. Bustamante ◽  
Yann R. Chemla ◽  
Shixin Liu ◽  
Michelle D. Wang
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Single Molecule Biophysics

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.

Molecular Motors: Force and Movement Generated by Single Myosin II Molecules

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 213-218 ◽  
Author(s):  
Caspar Rüegg ◽  
Claudia Veigel ◽  
Justin E. Molloy ◽  
Stephan Schmitz ◽  
John C. Sparrow ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Force Production ◽  
Myosin Isoforms ◽  
Single Molecule Level ◽  
Recent Developments ◽  
Muscle Myosin

Muscle myosin II is an ATP-driven, actin-based molecular motor. Recent developments in optical tweezers technology have made it possible to study movement and force production on the single-molecule level and to find out how different myosin isoforms may have adapted to their specific physiological roles.

scholarly journals Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor

2018 ◽  
Vol 115 (46) ◽  
pp. 11688-11693 ◽  
Author(s):  
Thomas Suren ◽  
Daniel Rutz ◽  
Patrick Mößmer ◽  
Ulrich Merkel ◽  
Johannes Buchner ◽  
...  
Keyword(s):  
Free Energy ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Optical Tweezers ◽  
Single Molecule ◽  
Mechanical Load ◽  
Force Spectroscopy ◽  
Folding Pathway ◽  
Hormone Binding ◽  
Single Molecule Force Spectroscopy

The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a “lid” structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of 41 kBT (24 kcal/mol). The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional 12 kBT of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s−1. From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.

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