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Special Issue "Gene Expression and Chromatin Biology 2.0"

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

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editors

Dr. Markus Proft
E-Mail Website
Guest Editor
CSIC-Instituto de Biomedicina de Valencia (IBV), Valencia, Spain
Interests: stress adaptation; gene expression; signal transduction; mitochondrial homeostasis; yeast
Special Issues and Collections in MDPI journals
Dr. Amparo Pascual-Ahuir
E-Mail Website
Guest Editor
Instituto de Biología Molecular y Celular de Plantas (IBMCP UPV-CSIC), Universidad Politécnica de Valencia, Valencia, Spain
Interests: stress adaptation; gene expression; signal transduction; mitochondrial homeostasis; yeast
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

This is the second edition of the Special Issue "Gene Expression and Chromatin Biology". The success of the first edition has motivated us to this new opening to capture still more interesting contributions to the field of chromatin biology and eukaryotic gene regulation.

This Special Issue on “Gene Expression and Chromatin Biology 2.0” will include recent experimental papers as well as timely review articles centered around the regulation of gene expression in eukaryotic organisms. The dynamic regulation of gene expression is a fundamental process of the cell, which impacts on its adaptation and survival upon environmental changes and on the execution of developmental programs. This field of investigation has experienced many technical advances in recent years, including the precise mapping of the interactions between transcriptionally engaged proteins with chromatin, determination of the dynamic nature of histone modifications and nucleosome movements, and the visualization of the transcriptional process in real-time and at the single cell- and single transcript-level, among others. Thus, we are getting closer to truly understanding the dynamic interplay of transcription factors, histone marks, basal transcription machinery, co-activator and co-repressor complexes, mRNA modification/export complexes, and how these components coordinate timely and fine-tuned responses of gene expression upon intrinsic and extrinsic cellular stimuli. We look forward to receiving your experimental papers, focused reviews within this fascinating research topic.

Dr. Markus Proft
Dr. Amparo Pascual-Ahuir
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 papers will be 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.

Keywords

  • gene expression
  • transcriptional regulation
  • chromatin
  • transcription factor
  • histone modification

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Published Papers (9 papers)

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Research

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Article
Yeast Translation Elongation Factor eIF5A Expression Is Regulated by Nutrient Availability through Different Signalling Pathways
Int. J. Mol. Sci. 2021, 22(1), 219; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010219 - 28 Dec 2020
Cited by 2 | Viewed by 864
Abstract
Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is [...] Read more.
Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is abundant and implicated in some cancer types; the eIF5A-2 isoform is absent in most cells but becomes overexpressed in many metastatic cancers. Several reports have connected eIF5A and mitochondria because it co-purifies with the organelle or its inhibition reduces respiration and mitochondrial enzyme levels. However, the mechanisms of eIF5A mitochondrial function, and whether eIF5A expression is regulated by the mitochondrial metabolism, are unknown. We analysed the expression of yeast eIF5A isoforms Tif51A and Tif51B under several metabolic conditions and in mutants. The depletion of Tif51A, but not Tif51B, compromised yeast growth under respiration and reduced oxygen consumption. Tif51A expression followed dual positive regulation: by high glucose through TORC1 signalling, like other translation factors, to promote growth and by low glucose or non-fermentative carbon sources through Snf1 and heme-dependent transcription factor Hap1 to promote respiration. Upon iron depletion, Tif51A was down-regulated and Tif51B up-regulated. Both were Hap1-dependent. Our results demonstrate eIF5A expression regulation by cellular metabolic status. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Article
In Vivo Validation of Alternative FDXR Transcripts in Human Blood in Response to Ionizing Radiation
Int. J. Mol. Sci. 2020, 21(21), 7851; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217851 - 23 Oct 2020
Cited by 7 | Viewed by 955
Abstract
Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific [...] Read more.
Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific quantitative real-time polymerase chain reaction (qPCR) primers were designed to establish dose-responses for eight curated FDXR variants, all up-regulated after IR in a dose-dependent manner. The potential role of gender on the expression of these variants was tested, and neither the variants response to IR nor the background level of expression was profoundly affected; moreover, in vitro induction of inflammation temporarily counteracted IR response early after exposure. Importantly, transcriptional up-regulation of these variants was further confirmed in vivo in blood of radiotherapy patients. Full-length nanopore sequencing was performed to identify other FDXR variants and revealed the high responsiveness of FDXR-201 and FDXR-208. Moreover, FDXR-218 and FDXR-219 showed no detectable endogenous expression, but a clear detection after IR. Overall, we characterised 14 FDXR transcript variants and identified for the first time their response to DNA damage in vivo. Future studies are required to unravel the function of these splicing variants, but they already represent a new class of radiation exposure biomarkers. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Article
CpG Site-Specific Regulation of Metallothionein-1 Gene Expression
Int. J. Mol. Sci. 2020, 21(17), 5946; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21175946 - 19 Aug 2020
Viewed by 950
Abstract
Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter [...] Read more.
Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter contains 5 MREs (a–e), and MTF1 has the highest affinity to MREd. Epigenetic changes like DNA methylation might affect transcription and, therefore, the cytoprotective function of MT genes. To reveal the CpG site(s) critical for Mt1 transcription, we analyzed the methylation status of CpG dinucleotides in the Mt1 gene promoter through bisulfite sequencing in P1798 mouse lymphosarcoma cells, with high or low MT expression. We found demethylated CpG sites near MREd and MREe, in cells with high expression. Next, we compared Mt1 gene-promoter-driven Lucia luciferase gene expression in unmethylated and methylated reporter vectors. To clarify the effect of complete and partial CpG methylation, we used M.SssI (CG→5mCG) and HhaI (GCGC→G5mCGC)-methylated reporter vectors. Point mutation analysis revealed that methylation of a CpG site near MREd and MREe strongly inhibited Mt1 gene expression. Our results suggest that the methylation status of this site is important for the regulation of Mt1 gene expression. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Article
Genome-Wide Characterization of GRAS Family and Their Potential Roles in Cold Tolerance of Cucumber (Cucumis sativus L.)
Int. J. Mol. Sci. 2020, 21(11), 3857; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21113857 - 29 May 2020
Cited by 5 | Viewed by 1237
Abstract
Cucumber (Cucumis sativus L.) is one of the most important cucurbit vegetables but is often subjected to stress during cultivation. GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) genes encode a family of transcriptional factors that regulate plant growth [...] Read more.
Cucumber (Cucumis sativus L.) is one of the most important cucurbit vegetables but is often subjected to stress during cultivation. GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) genes encode a family of transcriptional factors that regulate plant growth and development. In the model plant Arabidopsis thaliana, GRAS family genes function in formation of axillary meristem and root radial structure, phytohormone (gibberellin) signal transduction, light signal transduction and abiotic/biological stress. In this study, a gene family was comprehensively analyzed from the aspects of evolutionary tree, gene structure, chromosome location, evolutionary and expression pattern by means of bioinformatics; 37 GRAS gene family members have been screened from cucumber. We reconstructed an evolutionary tree based on multiple sequence alignment of the typical GRAS domain and conserved motif sequences with those of other species (A. thaliana and Solanum lycopersicum). Cucumber GRAS family was divided into 10 groups according to the classification of Arabidopsis and tomato genes. We conclude that tandem and segmental duplication have played important roles in the expansion and evolution of the cucumber GRAS (CsaGRAS) family. Expression patterns of CsaGRAS genes in different tissues and under cold treatment, combined with gene ontology annotation and interaction network analysis, revealed potentially different functions for CsaGRAS genes in response to cold tolerance, with members of the SHR, SCR and DELLA subfamilies likely playing important roles. In conclusion, this study provides valuable information and candidate genes for improving cucumber tolerance to cold stress. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Article
A Single Amino Acid Change in Nramp6 from Sedum Alfredii Hance Affects Cadmium Accumulation
Int. J. Mol. Sci. 2020, 21(9), 3169; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093169 - 30 Apr 2020
Viewed by 890
Abstract
SaNramp6 in Sedum alfredii encodes a membrane-localized metal transporter. We isolated the SaNramp6h allele from the hyperaccumulating ecotype (HE) of S. alfredii. When this allele was expressed in transgenic yeast and Arabidopsis thaliana, it enhanced their cadmium (Cd) sensitivity by increased [...] Read more.
SaNramp6 in Sedum alfredii encodes a membrane-localized metal transporter. We isolated the SaNramp6h allele from the hyperaccumulating ecotype (HE) of S. alfredii. When this allele was expressed in transgenic yeast and Arabidopsis thaliana, it enhanced their cadmium (Cd) sensitivity by increased Cd transport and accumulation. We isolated another allele, SaNramp6n, from a nonhyperaccumulating ecotype (NHE) of S. alfredii. Amino acid sequence comparisons revealed three amino acid differences between SaNramp6h and SaNramp6n. We investigated the Cd transport activity of the Nramp6 allele, and determined which residues are essential for the transport activity. We conducted structure-function analyses of SaNramp6 based on site-directed mutagenesis and functional assays of the mutants in yeast and Arabidopsis. The three residues that differed between SaNramp6h and SaNramp6n were mutated. Only the L157P mutation of SaNramp6h impaired Cd transport. The other mutations, S218N and T504A, did not affect the transport activity of SaNramp6h, indicating that these residues are not essential for metal selectivity. Transgenic plants overexpressing SaNramp6hL157P showed altered metal accumulation in shoots and roots. Our results suggest that the conserved site L157 is essential for the high metal transport activity of SaNramp6h. This information may be useful for limiting or increasing Cd transport by other plant natural resistance associated macrophage protein (NRAMP) proteins. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Review

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Review
Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia
Int. J. Mol. Sci. 2021, 22(6), 3127; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063127 - 18 Mar 2021
Viewed by 785
Abstract
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the [...] Read more.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the deregulation of chromatin remodelers. This review considers in depth how the alteration of epigenetic profiles (at DNA and histone levels) induces an aberrant phenotype in B lymphocyte progenitors by modulating the oncogenic drivers and tumor suppressors involved in key cancer hallmarks. DNA methylation patterns have been widely studied in BCP-ALL and their correlation with survival has been established. However, the effect of methylation on histone residues can be very different. For instance, methyltransferase KMT2A gene participates in chromosomal rearrangements with several partners, imposing an altered pattern of methylated H3K4 and H3K79 residues, enhancing oncogene promoter activation, and conferring a worse outcome on affected infants. In parallel, acetylation processes provide an additional layer of epigenetic regulation and can alter the chromatin conformation, enabling the binding of regulatory factors. Therefore, an integrated knowledge of all epigenetic disorders is essential to understand the molecular basis of BCP-ALL and to identify novel entry points that can be exploited to improve therapeutic options and disease prognosis. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Review
Multifaceted Chromatin Structure and Transcription Changes in Plant Stress Response
Int. J. Mol. Sci. 2021, 22(4), 2013; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042013 - 18 Feb 2021
Cited by 1 | Viewed by 1072
Abstract
Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are [...] Read more.
Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are epigenetically regulated and are required for stress-induced transcriptional regulation or reprogramming. Epigenetic regulators facilitate the phenotypic plasticity of development and the survival and reproduction of plants in unfavorable environments, and they are highly diversified, including histone and DNA modifiers, histone variants, chromatin remodelers, and regulatory non-coding RNAs. They contribute to chromatin modifications, remodeling and dynamics, and constitute a multilayered and multifaceted circuitry for sophisticated and robust epigenetic regulation of plant stress responses. However, this complicated epigenetic regulatory circuitry creates challenges for elucidating the common or differential roles of chromatin modifications for transcriptional regulation or reprogramming in different plant stress responses. Particularly, interacting chromatin modifications and heritable stress memories are difficult to identify in the aspect of chromatin-based epigenetic regulation of transcriptional reprogramming and memory. Therefore, this review discusses the recent updates from the three perspectives—stress specificity or dependence of transcriptional reprogramming, the interplay of chromatin modifications, and transcriptional stress memory in plants. This helps solidify our knowledge on chromatin-based transcriptional reprogramming for plant stress response and memory. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Review
Capturing and Understanding the Dynamics and Heterogeneity of Gene Expression in the Living Cell
Int. J. Mol. Sci. 2020, 21(21), 8278; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218278 - 05 Nov 2020
Viewed by 690
Abstract
The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in gene expression are highly dynamic and depend on many intrinsic and extrinsic factors. In this review, we highlight [...] Read more.
The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in gene expression are highly dynamic and depend on many intrinsic and extrinsic factors. In this review, we highlight the dynamic nature of transient gene expression changes to better understand cell physiology and development in general. We will start by comparing recent in vivo procedures to capture gene expression in real time. Intrinsic factors modulating gene expression dynamics will then be discussed, focusing on chromatin modifications. Furthermore, we will dissect how cell physiology or age impacts on dynamic gene regulation and especially discuss molecular insights into acquired transcriptional memory. Finally, this review will give an update on the mechanisms of heterogeneous gene expression among genetically identical individual cells. We will mainly focus on state-of-the-art developments in the yeast model but also cover higher eukaryotic systems. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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Review
Sharing Marks: H3K4 Methylation and H2B Ubiquitination as Features of Meiotic Recombination and Transcription
Int. J. Mol. Sci. 2020, 21(12), 4510; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124510 - 25 Jun 2020
Cited by 3 | Viewed by 1877
Abstract
Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) [...] Read more.
Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) and their repair using homologous chromosomes are essential and highly regulated pathways. Similar to other processes that take place in the context of chromatin, histone posttranslational modifications (PTMs) constitute one of the major mechanisms to regulate meiotic recombination. In this review, we focus on specific PTMs occurring in histone tails as driving forces of different molecular events, including meiotic recombination and transcription. In particular, we concentrate on the influence of H3K4me3, H2BK123ub, and their corresponding molecular machineries that write, read, and erase these histone marks. The Spp1 subunit within the Complex of Proteins Associated with Set1 (COMPASS) is a critical regulator of H3K4me3-dependent meiotic DSB formation. On the other hand, the PAF1c (RNA polymerase II associated factor 1 complex) drives the ubiquitination of H2BK123 by Rad6-Bre1. We also discuss emerging evidence obtained by cryo-electron microscopy (EM) structure determination that has provided new insights into how the “cross-talk” between these two marks is accomplished. Full article
(This article belongs to the Special Issue Gene Expression and Chromatin Biology)
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