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Positioning of Nucleosomes
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Positioning of Nucleosomes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (15 April 2021) | Viewed by 20441

Special Issue Editor

Dr. Tobias Straub

E-Mail Website
Guest Editor
Biomedical Center - Bioinformatics, Ludwig-Maximilians-Universität München, Munich, Germany
Interests: functional genomics; biostatistis; chromatin biology; metabolism; open science; translational life science; digital health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Nucleosomes consisting of core histone proteins with about 150 bp DNA wrapped around are the building blocks of chromatin. Their relative positioning along the DNA is thought to have strong impact on transcription factor binding and DNA templated processes. Furthermore, the ensemble configuration characterised by the spacing of consecutive nucleosomes influences the steric organisation of the chromatin fibre. There is great interest in elucidating the principles that both fix nucleosomes at specific sites and relocate them for regulating genome activity. Biochemical in vitro assays, functional analyses at specific genomic target sites, genome-wide nucleosome mapping and high dimensional bioinformatic analyses constitute a plethora of approaches that further our knowledge on the interplay between nucleosome positions, DNA sequence, histone variants and modifications and the functional state of the genome.

This Special Issue, “Nucleosome positioning”, will cover a selection of recent research topics and current review articles in the field of chromatin biology with a specific focus on the rules and processes that define the positions of nucleosomes as well as their functional implications.

Potential topics include, but are not limited to:

Nucleosome positioning sequences

Nucleosome positions & histone modifications / variants

Nucleosome remodeler defining nucleosome positions

Nucleosomal arrays

Mapping nucleosome positions

Gene expression regulation by nucleosome positioning

Nucleosome positioning and genome integrity

Dr. Tobias Straub
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Related Special Issue

Published Papers (6 papers)

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Research

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20 pages, 3512 KiB  
Communication
The Active Mechanism of Nucleosome Depletion by Poly(dA:dT) Tracts In Vivo
by Toby Barnes and Philipp Korber
Int. J. Mol. Sci. 2021, 22(15), 8233; https://doi.org/10.3390/ijms22158233 - 30 Jul 2021
Cited by 8 | Viewed by 2311
Abstract
Poly(dA:dT) tracts cause nucleosome depletion in many species, e.g., at promoters and replication origins. Their intrinsic biophysical sequence properties make them stiff and unfavorable for nucleosome assembly, as probed by in vitro nucleosome reconstitution. The mere correlation between nucleosome depletion over poly(dA:dT) tracts [...] Read more.
Poly(dA:dT) tracts cause nucleosome depletion in many species, e.g., at promoters and replication origins. Their intrinsic biophysical sequence properties make them stiff and unfavorable for nucleosome assembly, as probed by in vitro nucleosome reconstitution. The mere correlation between nucleosome depletion over poly(dA:dT) tracts in in vitro reconstituted and in in vivo chromatin inspired an intrinsic nucleosome exclusion mechanism in vivo that is based only on DNA and histone properties. However, we compile here published and new evidence that this correlation does not reflect mechanistic causation. (1) Nucleosome depletion over poly(dA:dT) in vivo is not universal, e.g., very weak in S. pombe. (2) The energy penalty for incorporating poly(dA:dT) tracts into nucleosomes is modest (<10%) relative to ATP hydrolysis energy abundantly invested by chromatin remodelers. (3) Nucleosome depletion over poly(dA:dT) is much stronger in vivo than in vitro if monitored without MNase and (4) actively maintained in vivo. (5) S. cerevisiae promoters evolved a strand-biased poly(dA) versus poly(dT) distribution. (6) Nucleosome depletion over poly(dA) is directional in vivo. (7) The ATP dependent chromatin remodeler RSC preferentially and directionally displaces nucleosomes towards 5′ of poly(dA). Especially distribution strand bias and displacement directionality would not be expected for an intrinsic mechanism. Together, this argues for an in vivo mechanism where active and species-specific read out of intrinsic sequence properties, e.g., by remodelers, shapes nucleosome organization. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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12 pages, 1172 KiB  
Article
The Role of Non-Catalytic Domains of Hrp3 in Nucleosome Remodeling
by Wenbo Dong, Punit Prasad, Andreas Lennartsson and Karl Ekwall
Int. J. Mol. Sci. 2021, 22(4), 1793; https://doi.org/10.3390/ijms22041793 - 11 Feb 2021
Viewed by 1892
Abstract
The Helicase-related protein 3 (Hrp3), an ATP-dependent chromatin remodeling enzyme from the CHD family, is crucial for maintaining global nucleosome occupancy in Schizosaccharomyces pombe (S. pombe). Although the ATPase domain of Hrp3 is essential for chromatin remodeling, the contribution of non-ATPase [...] Read more.
The Helicase-related protein 3 (Hrp3), an ATP-dependent chromatin remodeling enzyme from the CHD family, is crucial for maintaining global nucleosome occupancy in Schizosaccharomyces pombe (S. pombe). Although the ATPase domain of Hrp3 is essential for chromatin remodeling, the contribution of non-ATPase domains of Hrp3 is still unclear. Here, we investigated the role of non-ATPase domains using in vitro methods. In our study, we expressed and purified recombinant S. pombe histone proteins, reconstituted them into histone octamers, and assembled nucleosome core particles. Using reconstituted nucleosomes and affinity-purified wild type and mutant Hrp3 from S. pombe we created a homogeneous in vitro system to evaluate the ATP hydrolyzing capacity of truncated Hrp3 proteins. We found that all non-ATPase domain deletions (∆chromo, ∆SANT, ∆SLIDE, and ∆coupling region) lead to reduced ATP hydrolyzing activities in vitro with DNA or nucleosome substrates. Only the coupling region deletion showed moderate stimulation of ATPase activity with the nucleosome. Interestingly, affinity-purified Hrp3 showed co-purification with all core histones suggesting a strong association with the nucleosomes in vivo. However, affinity-purified Hrp3 mutant with SANT and coupling regions deletion showed complete loss of interactions with the nucleosomes, while SLIDE and chromodomain deletions reduced Hrp3 interactions with the nucleosomes. Taken together, nucleosome association and ATPase stimulation by DNA or nucleosomes substrate suggest that the enzymatic activity of Hrp3 is fine-tuned by unique contributions of all four non-catalytic domains. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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20 pages, 2513 KiB  
Article
JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions
by Tara Procida, Tobias Friedrich, Antonia P. M. Jack, Martina Peritore, Clemens Bönisch, H. Christian Eberl, Nadine Daus, Konstantin Kletenkov, Andrea Nist, Thorsten Stiewe, Tilman Borggrefe, Matthias Mann, Marek Bartkuhn and Sandra B. Hake
Int. J. Mol. Sci. 2021, 22(2), 678; https://doi.org/10.3390/ijms22020678 - 12 Jan 2021
Cited by 12 | Viewed by 4280
Abstract
Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While [...] Read more.
Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1’s function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60’s enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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Review

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37 pages, 4997 KiB  
Review
Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer
by Cedric R. Clapier
Int. J. Mol. Sci. 2021, 22(11), 5578; https://doi.org/10.3390/ijms22115578 - 25 May 2021
Cited by 22 | Viewed by 4454
Abstract
The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific [...] Read more.
The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. In this review, I first present the functional and structural diversity of remodelers, while emphasizing the basic mechanism of DNA translocation, the common regulatory aspects, and the hand-in-hand progressive increase in complexity of the regulatory conversations between remodelers and nucleosomes that accompanies the increase in challenges of remodeling processes. Next, I examine how, through nucleosome positioning, remodelers guide the regulation of gene expression. Finally, I explore various aspects of how alterations/mutations in remodelers introduce dissonance into the conversations between remodelers and nucleosomes, modify chromatin organization, and contribute to oncogenesis. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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18 pages, 566 KiB  
Review
Peculiarities of Plasmodium falciparum Gene Regulation and Chromatin Structure
by Maria Theresia Watzlowik, Sujaan Das, Markus Meissner and Gernot Längst
Int. J. Mol. Sci. 2021, 22(10), 5168; https://doi.org/10.3390/ijms22105168 - 13 May 2021
Cited by 4 | Viewed by 2923
Abstract
The highly complex life cycle of the human malaria parasite, Plasmodium falciparum, is based on an orchestrated and tightly regulated gene expression program. In general, eukaryotic transcription regulation is determined by a combination of sequence-specific transcription factors binding to regulatory DNA elements [...] Read more.
The highly complex life cycle of the human malaria parasite, Plasmodium falciparum, is based on an orchestrated and tightly regulated gene expression program. In general, eukaryotic transcription regulation is determined by a combination of sequence-specific transcription factors binding to regulatory DNA elements and the packaging of DNA into chromatin as an additional layer. The accessibility of regulatory DNA elements is controlled by the nucleosome occupancy and changes of their positions by an active process called nucleosome remodeling. These epigenetic mechanisms are poorly explored in P. falciparum. The parasite genome is characterized by an extraordinarily high AT-content and the distinct architecture of functional elements, and chromatin-related proteins also exhibit high sequence divergence compared to other eukaryotes. Together with the distinct biochemical properties of nucleosomes, these features suggest substantial differences in chromatin-dependent regulation. Here, we highlight the peculiarities of epigenetic mechanisms in P. falciparum, addressing chromatin structure and dynamics with respect to their impact on transcriptional control. We focus on the specialized chromatin remodeling enzymes and discuss their essential function in P. falciparum gene regulation. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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19 pages, 2028 KiB  
Review
Chromatin Remodeling in the Brain-a NuRDevelopmental Odyssey
by Sarah Larrigan, Sujay Shah, Alex Fernandes and Pierre Mattar
Int. J. Mol. Sci. 2021, 22(9), 4768; https://doi.org/10.3390/ijms22094768 - 30 Apr 2021
Cited by 8 | Viewed by 3132
Abstract
During brain development, the genome must be repeatedly reconfigured in order to facilitate neuronal and glial differentiation. A host of chromatin remodeling complexes facilitates this process. At the genetic level, the non-redundancy of these complexes suggests that neurodevelopment may require a lexicon of [...] Read more.
During brain development, the genome must be repeatedly reconfigured in order to facilitate neuronal and glial differentiation. A host of chromatin remodeling complexes facilitates this process. At the genetic level, the non-redundancy of these complexes suggests that neurodevelopment may require a lexicon of remodelers with different specificities and activities. Here, we focus on the nucleosome remodeling and deacetylase (NuRD) complex. We review NuRD biochemistry, genetics, and functions in neural progenitors and neurons. Full article
(This article belongs to the Special Issue Positioning of Nucleosomes)
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