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Cells
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Epigenetics, Chromatin Structure and Transcription Regulation
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Epigenetics, Chromatin Structure and Transcription Regulation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 7753

Special Issue Editors

Prof. Dr. Jop Kind

E-Mail Website
Guest Editor
Oncode Institute, Hubrecht Institute–KNAW and University Medical Center Utrecht, 3584 Utrecht, The Netherlands
Interests: single-cell genomics;epigenetics; spatial genome organization; bioinformatics; gene-regulation; embryogenesis; tumorigenesis
Dr. Daan Noordermeer

E-Mail Website
Guest Editor
Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
Interests: 3D genome organization; epigenetic domains and architectural proteins work together to regulate gene activity

Special Issue Information

Dear Colleagues,

The spatiotemporal coordination of gene expression is achieved through the concerted activity of a wide-range of factors and mechanisms that act on different genomic scales. On a larger scale, chromosomes are organized into domains of similar chromatin states, which are positioned at non-random positions within the nuclear space. At intermediate levels, DNA loops are formed that are constrained within topologically associating domains (TADs). At the local level, DNA methylation, histone tail modifications, and chromatin remodeling complexes synergistically modulate interactions between promoters and transcription factors, and thereby regulate gene activity. The collective action of all of these components ultimately determines cellular identity and function, and when misregulated can result in malignant phenotypes.

The ever-evolving developments in microscopy and genomics technologies have enabled the measurement of a multitude of modalities in the same cell or tissue, over time and on the same molecule, thereby starting to provide possibilities to determine the interdependencies of multifaceted gene activity control. These studies are further aided by the development of versatile systems to selectively, conditionally, and acutely deplete proteins, or otherwise manipulate their functions. In parallel, the application of increasingly advanced computational simulations, machine learning algorithms, and biophysical modeling approaches provides means with which to make predictions about the underlying mechanisms, thereby opening up hypotheses for experimental validation.

This Special Issue will be devoted to research into chromatin structure, epigenetics, the organization of the genome within the nucleus, and the coordination of nuclear processes, with an emphasis on the spatiotemporal control of gene transcription.

Prof. Dr. Jop Kind
Dr. Daan Noordermeer
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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.

Keywords

  • three-dimensional genome organization
  • nucleosomes and chromatin structure
  • epigenetics/histone modications
  • transcription factor networks
  • imprinting/X inactivation
  • zygotic genome activation
  • pioneer transcription factors and mitotic bookmarking
  • evolution of nuclear processes and transcriptional regulation
  • heterogeneity of nuclear processes and transcriptional regulation:
    • single-cell and spatial-omics
    • super-resolution and live-cell imaging
    • structural biology and single-molecule sequencing.
  • computational biology, machine learning and simulations, and biophysical modeling for nuclear processes as well as transcriptional regulation

Published Papers (4 papers)

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Research

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15 pages, 2037 KiB  
Article
Identification and Characterization of HIRIP3 as a Histone H2A Chaperone
by Maria Ignatyeva, Abdul Kareem Mohideen Patel, Abdulkhaleg Ibrahim, Raed S. Albiheyri, Ali T. Zari, Ahmed Bahieldin, Christian Bronner, Jamal S. M. Sabir and Ali Hamiche
Cells 2024, 13(3), 273; https://doi.org/10.3390/cells13030273 - 1 Feb 2024
Viewed by 987
Abstract
HIRIP3 is a mammalian protein homologous to the yeast H2A.Z deposition chaperone Chz1. However, the structural basis underlying Chz’s binding preference for H2A.Z over H2A, as well as the mechanism through which Chz1 modulates histone deposition or replacement, remains enigmatic. In this study, [...] Read more.
HIRIP3 is a mammalian protein homologous to the yeast H2A.Z deposition chaperone Chz1. However, the structural basis underlying Chz’s binding preference for H2A.Z over H2A, as well as the mechanism through which Chz1 modulates histone deposition or replacement, remains enigmatic. In this study, we aimed to characterize the function of HIRIP3 and to identify its interacting partners in HeLa cells. Our findings reveal that HIRIP3 is specifically associated in vivo with H2A–H2B dimers and CK2 kinase. While bacterially expressed HIRIP3 exhibited a similar binding affinity towards H2A and H2A.Z, the associated CK2 kinase showed a notable preference for H2A phosphorylation at serine 1. The recombinant HIRIP3 physically interacted with the H2A αC helix through an extended CHZ domain and played a crucial role in depositing the canonical core histones onto naked DNA. Our results demonstrate that mammalian HIRIP3 acts as an H2A histone chaperone, assisting in its selective phosphorylation by Ck2 kinase at serine 1 and facilitating its deposition onto chromatin. Full article
(This article belongs to the Special Issue Epigenetics, Chromatin Structure and Transcription Regulation)
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17 pages, 2912 KiB  
Article
Recruitment of the Histone Variant MacroH2A1 to the Pericentric Region Occurs upon Chromatin Relaxation and Is Responsible for Major Satellite Transcriptional Regulation
by Ludmila Recoules, Nicolas Tanguy Le Gac, Fatima Moutahir, Kerstin Bystricky and Anne-Claire Lavigne
Cells 2023, 12(17), 2175; https://doi.org/10.3390/cells12172175 - 30 Aug 2023
Viewed by 872
Abstract
Heterochromatin formation plays a pivotal role in regulating chromatin organization and influences nuclear architecture and genome stability and expression. Amongst the locations where heterochromatin is found, the pericentric regions have the capability to attract the histone variant macroH2A1. However, the factors and mechanisms [...] Read more.
Heterochromatin formation plays a pivotal role in regulating chromatin organization and influences nuclear architecture and genome stability and expression. Amongst the locations where heterochromatin is found, the pericentric regions have the capability to attract the histone variant macroH2A1. However, the factors and mechanisms behind macroH2A1 incorporation into these regions have not been explored. In this study, we probe different conditions that lead to the recruitment of macroH2A1 to pericentromeric regions and elucidate its underlying functions. Through experiments conducted on murine fibroblastic cells, we determine that partial chromatin relaxation resulting from DNA damage, senescence, or histone hyper-acetylation is necessary for the recruitment of macroH2A1 to pericentric regions. Furthermore, macroH2A1 is required for upregulation of noncoding pericentric RNA expression but not for pericentric chromatin organization. Our findings shed light on the functional rather than structural significance of macroH2A1 incorporation into pericentric chromatin. Full article
(This article belongs to the Special Issue Epigenetics, Chromatin Structure and Transcription Regulation)
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Review

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16 pages, 2975 KiB  
Review
The Material Properties of the Cell Nucleus: A Matter of Scale
by Maud Hertzog and Fabian Erdel
Cells 2023, 12(15), 1958; https://doi.org/10.3390/cells12151958 - 28 Jul 2023
Cited by 2 | Viewed by 2224
Abstract
Chromatin regulatory processes physically take place in the environment of the cell nucleus, which is filled with the chromosomes and a plethora of smaller biomolecules. The nucleus contains macromolecular assemblies of different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, [...] Read more.
Chromatin regulatory processes physically take place in the environment of the cell nucleus, which is filled with the chromosomes and a plethora of smaller biomolecules. The nucleus contains macromolecular assemblies of different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, and nuclear bodies. This multiscale organization impacts the transport processes within the nuclear interior, the global mechanical properties of the nucleus, and the way the nucleus senses and reacts to mechanical stimuli. Here, we discuss recent work on these aspects, including microrheology and micromanipulation experiments assessing the material properties of the nucleus and its subcomponents. We summarize how the properties of multiscale media depend on the time and length scales probed in the experiment, and we reconcile seemingly contradictory observations made on different scales. We also revisit the concept of liquid-like and solid-like material properties for complex media such as the nucleus. We propose that the nucleus can be considered a multiscale viscoelastic medium composed of three major components with distinct properties: the lamina, the chromatin network, and the nucleoplasmic fluid. This multicomponent organization enables the nucleus to serve its different functions as a reaction medium on the nanoscale and as a mechanosensor and structural scaffold on the microscale. Full article
(This article belongs to the Special Issue Epigenetics, Chromatin Structure and Transcription Regulation)
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33 pages, 2236 KiB  
Review
Experimental Validation and Prediction of Super-Enhancers: Advances and Challenges
by Ekaterina V. Kravchuk, German A. Ashniev, Marina G. Gladkova, Alexey V. Orlov, Anastasiia V. Vasileva, Anna V. Boldyreva, Alexandr G. Burenin, Artemiy M. Skirda, Petr I. Nikitin and Natalia N. Orlova
Cells 2023, 12(8), 1191; https://doi.org/10.3390/cells12081191 - 19 Apr 2023
Cited by 1 | Viewed by 3073
Abstract
Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and [...] Read more.
Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and tumorigenesis. Our goal was to systematize research studies dedicated to the investigation of structure and functions of super-enhancers as well as to define further perspectives of the field in various applications, such as drug development and clinical use. We overviewed the fundamental studies which provided experimental data on various pathologies and their associations with particular super-enhancers. The analysis of mainstream approaches for SE search and prediction allowed us to accumulate existing data and propose directions for further algorithmic improvements of SEs’ reliability levels and efficiency. Thus, here we provide the description of the most robust algorithms such as ROSE, imPROSE, and DEEPSEN and suggest their further use for various research and development tasks. The most promising research direction, which is based on topic and number of published studies, are cancer-associated super-enhancers and prospective SE-targeted therapy strategies, most of which are discussed in this review. Full article
(This article belongs to the Special Issue Epigenetics, Chromatin Structure and Transcription Regulation)
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