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Disentangling Mechanisms of Genomic Regulation of Cell Functions at the...
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Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 30991

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Hans Binder

E-Mail Website
Guest Editor
Interdisciplinary Centre for Bioinformatics, Leipzig University, Haertelstr. 16–18, D-04107 Leipzig, Germany
Interests: genome medicine; computational biology; genomic regulation
Special Issues, Collections and Topics in MDPI journals
Dr. Arsen Arakelyan

E-Mail Website
Guest Editor
Institute for Molecular Biology, Academy of sciences of the Republic of Armenia, Yerevan, 7 Hasratyan Str, 0014, Armenia
Interests: computations biology; transcriptomics; biological pathways; omics data analysis applications

Special Issue Information

Dear Colleagues,

Genomic regulation is at the origin of cellular processes in healthy and diseased states. The advent of sequencing and other high-throughput molecular techniques, in combination with the accumulation of omics data and the development of bioinformatics methods, has led to considerable progress in understanding the genomic regulation of cell states and, particularly, the role of single genes and of their mutual interactions in health and disease.

In this Special Issue, we welcome reviews, reports of new methods, and original articles covering all aspects of the genomic regulation of cell functions at the gene level.

Dr. Hans Binder
Dr. Arsen Arakelyan
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. Genes is an international peer-reviewed open access monthly 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 2600 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

  • Genomic regulation of development, differentiation and ageing
  • Mechanisms of genomic, transcriptomic, and epigenomic dysregulation in diseases (for example, cancer, inflammatory and autoimmune diseases)
  • Genomic (e.g., mutations,), transcriptional (e.g., alternative splicing), epigenetic (e.g., DNA methylation, histone modifications) and proteomic levels of regulation and their mutual couplings
  • Gene networks and pathways
  • Computational and conceptional models
  • Transcriptional, post-transcriptional, translational mechanisms
  • Omics data analyses, single-cell sequencing
  • Bioinformatics approaches (including machine learning) to understand genomic regulation
  • Integrative analysis of multi-omics data
  • Population genomics of diseases and traits with impact for gene function
  • Gene-level and pathway models of telomere regulation and of other cell functions

Published Papers (8 papers)

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Editorial

Jump to: Research, Review

3 pages, 166 KiB  
Editorial
Special Issue “Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level”
by Hans Binder and Arsen Arakelyan
Genes 2020, 11(12), 1463; https://doi.org/10.3390/genes11121463 - 07 Dec 2020
Viewed by 1561
Abstract
The term “gene” was introduced more than a hundred years ago to define a “fundamental physical and functional unit of heredity” [...] Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)

Research

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21 pages, 4241 KiB  
Article
Developmental scRNAseq Trajectories in Gene- and Cell-State Space—The Flatworm Example
by Maria Schmidt, Henry Loeffler-Wirth and Hans Binder
Genes 2020, 11(10), 1214; https://doi.org/10.3390/genes11101214 - 16 Oct 2020
Cited by 12 | Viewed by 3868
Abstract
Single-cell RNA sequencing has become a standard technique to characterize tissue development. Hereby, cross-sectional snapshots of the diversity of cell transcriptomes were transformed into (pseudo-) longitudinal trajectories of cell differentiation using computational methods, which are based on similarity measures distinguishing cell phenotypes. Cell [...] Read more.
Single-cell RNA sequencing has become a standard technique to characterize tissue development. Hereby, cross-sectional snapshots of the diversity of cell transcriptomes were transformed into (pseudo-) longitudinal trajectories of cell differentiation using computational methods, which are based on similarity measures distinguishing cell phenotypes. Cell development is driven by alterations of transcriptional programs e.g., by differentiation from stem cells into various tissues or by adapting to micro-environmental requirements. We here complement developmental trajectories in cell-state space by trajectories in gene-state space to more clearly address this latter aspect. Such trajectories can be generated using self-organizing maps machine learning. The method transforms multidimensional gene expression patterns into two dimensional data landscapes, which resemble the metaphoric Waddington epigenetic landscape. Trajectories in this landscape visualize transcriptional programs passed by cells along their developmental paths from stem cells to differentiated tissues. In addition, we generated developmental “vector fields” using RNA-velocities to forecast changes of RNA abundance in the expression landscapes. We applied the method to tissue development of planarian as an illustrative example. Gene-state space trajectories complement our data portrayal approach by (pseudo-)temporal information about changing transcriptional programs of the cells. Future applications can be seen in the fields of tissue and cell differentiation, ageing and tumor progression and also, using other data types such as genome, methylome, and also clinical and epidemiological phenotype data. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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22 pages, 4221 KiB  
Article
SOMmelier—Intuitive Visualization of the Topology of Grapevine Genome Landscapes Using Artificial Neural Networks
by Maria Nikoghosyan, Maria Schmidt, Kristina Margaryan, Henry Loeffler-Wirth, Arsen Arakelyan and Hans Binder
Genes 2020, 11(7), 817; https://doi.org/10.3390/genes11070817 - 17 Jul 2020
Cited by 8 | Viewed by 3826
Abstract
Background: Whole-genome studies of vine cultivars have brought novel knowledge about the diversity, geographical relatedness, historical origin and dissemination, phenotype associations and genetic markers. Method: We applied SOM (self-organizing maps) portrayal, a neural network-based machine learning method, to re-analyze the genome-wide Single Nucleotide [...] Read more.
Background: Whole-genome studies of vine cultivars have brought novel knowledge about the diversity, geographical relatedness, historical origin and dissemination, phenotype associations and genetic markers. Method: We applied SOM (self-organizing maps) portrayal, a neural network-based machine learning method, to re-analyze the genome-wide Single Nucleotide Polymorphism (SNP) data of nearly eight hundred grapevine cultivars. The method generates genome-specific data landscapes. Their topology reflects the geographical distribution of cultivars, indicates paths of cultivar dissemination in history and genome-phenotype associations about grape utilization. Results: The landscape of vine genomes resembles the geographic map of the Mediterranean world, reflecting two major dissemination paths from South Caucasus along a northern route via Balkan towards Western Europe and along a southern route via Palestine and Maghreb towards Iberian Peninsula. The Mediterranean and Black Sea, as well as the Pyrenees, constitute barriers for genetic exchange. On the coarsest level of stratification, cultivars divide into three major groups: Western Europe and Italian grapes, Iberian grapes and vine cultivars from Near East and Maghreb regions. Genetic landmarks were associated with agronomic traits, referring to their utilization as table and wine grapes. Pseudotime analysis describes the dissemination of grapevines in an East to West direction in different waves of cultivation. Conclusion: In analogy to the tasks of the wine waiter in gastronomy, the sommelier, our ‘SOMmelier’-approach supports understanding the diversity of grapevine genomes in the context of their geographic and historical background, using SOM portrayal. It offers an option to supplement vine cultivar passports by genome fingerprint portraits. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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16 pages, 2912 KiB  
Article
Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats
by Ivan B. Filippenkov, Vasily V. Stavchansky, Alina E. Denisova, Vadim V. Yuzhakov, Larisa E. Sevan’kaeva, Olga Y. Sudarkina, Veronika G. Dmitrieva, Leonid V. Gubsky, Nikolai F. Myasoedov, Svetlana A. Limborska and Lyudmila V. Dergunova
Genes 2020, 11(6), 681; https://doi.org/10.3390/genes11060681 - 22 Jun 2020
Cited by 17 | Viewed by 3717
Abstract
Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with [...] Read more.
Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia–reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia–reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia–reperfusion conditions. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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16 pages, 2180 KiB  
Article
Rising Roles of Small Noncoding RNAs in Cotranscriptional Regulation: In Silico Study of miRNA and piRNA Regulatory Network in Humans
by Massimiliano Chetta, Lorena Di Pietro, Nenad Bukvic and Wanda Lattanzi
Genes 2020, 11(5), 482; https://doi.org/10.3390/genes11050482 - 29 Apr 2020
Cited by 7 | Viewed by 3004
Abstract
Gene expression regulation is achieved through an intricate network of molecular interactions, in which trans-acting transcription factors (TFs) and small noncoding RNAs (sncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a key role. Recent observations allowed postulating an interplay between TFs and [...] Read more.
Gene expression regulation is achieved through an intricate network of molecular interactions, in which trans-acting transcription factors (TFs) and small noncoding RNAs (sncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a key role. Recent observations allowed postulating an interplay between TFs and sncRNAs, in that they may possibly share DNA-binding sites. The aim of this study was to analyze the complete subset of miRNA and piRNA sequences stored in the main databases in order to identify the occurrence of conserved motifs and subsequently predict a possible innovative interplay with TFs at a transcriptional level. To this aim, we adopted an original in silico workflow to search motifs and predict interactions within genome-scale regulatory networks. Our results allowed categorizing miRNA and piRNA motifs, with corresponding TFs sharing complementary DNA-binding motifs. The biological interpretation of the gene ontologies of the TFs permitted observing a selective enrichment in developmental pathways, allowing the distribution of miRNA motifs along a topological and chronological frame. In addition, piRNA motifs were categorized for the first time and revealed specific functional implications in somatic tissues. These data might pose experimental hypotheses to be tested in biological models, towards clarifying novel in gene regulatory routes. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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Review

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11 pages, 891 KiB  
Review
Features of DNA Repair in the Early Stages of Mammalian Embryonic Development
by Evgenia V. Khokhlova, Zoia S. Fesenko, Julia V. Sopova and Elena I. Leonova
Genes 2020, 11(10), 1138; https://doi.org/10.3390/genes11101138 - 27 Sep 2020
Cited by 27 | Viewed by 4950
Abstract
Cell repair machinery is responsible for protecting the genome from endogenous and exogenous effects that induce DNA damage. Mutations that occur in somatic cells lead to dysfunction in certain tissues or organs, while a violation of genomic integrity during the embryonic period often [...] Read more.
Cell repair machinery is responsible for protecting the genome from endogenous and exogenous effects that induce DNA damage. Mutations that occur in somatic cells lead to dysfunction in certain tissues or organs, while a violation of genomic integrity during the embryonic period often leads to death. A mammalian embryo’s ability to respond to damaged DNA and repair it, as well as its sensitivity to specific lesions, is still not well understood. In this review, we combine disparate data on repair processes in the early stages of preimplantation development in mammalian embryos. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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14 pages, 1937 KiB  
Review
The Metabolization Profile of the CYP2D6 Gene in Amerindian Populations: A Review
by Luciana P. C. Leitão, Tatiane P. Souza, Juliana C. G. Rodrigues, Marianne R. Fernandes, Sidney Santos and Ney P. C. Santos
Genes 2020, 11(3), 262; https://doi.org/10.3390/genes11030262 - 28 Feb 2020
Cited by 12 | Viewed by 3678
Abstract
Background: the CYP2D6 gene is clinically important and is known to have a number of variants. This gene has four distinct metabolization profiles that are determined by the different allelic forms present in the individual. The relative frequency of these profiles varies considerably [...] Read more.
Background: the CYP2D6 gene is clinically important and is known to have a number of variants. This gene has four distinct metabolization profiles that are determined by the different allelic forms present in the individual. The relative frequency of these profiles varies considerably among human populations around the world. Populations from more isolated regions, such as Native Americans, are still relatively poorly studied, however. Even so, recent advances in genotyping techniques and increasing interest in the study of these populations has led to a progressive increase in publication rates. Given this, the review presented here compiled the principal papers published on the CYP2D6 gene in Amerindian populations to determine the metabolic profile of this group. Methods: a systematic literature review was conducted in three scientific publication platforms (Google Scholar, Science Direct, and Pubmed). The search was run using the keywords “CYP2D6 Amerindians” and “CYP2D6 native Americans”. Results: a total of 13 original papers met the inclusion criteria established for this study. All the papers presented frequencies of the different CYP2D6 alleles in Amerindian populations. Seven of the papers focused specifically on Amerindian populations from Mexico, while the others included populations from Argentina, Chile, Costa Rica, Mexico, Paraguay, Peru, and the United States. The results of the papers reviewed here showed that the extensive metabolization profile was the most prevalent in all Amerindian populations studied to date, followed by the intermediate, slow, and ultra-rapid, in that order. Conclusion: the metabolization profiles of the Amerindian populations reviewed in the present study do not diverge in any major way from those of other populations from around the world. Given the paucity of the data available on Amerindian populations, further research is required to better characterize the metabolization profile of these populations to ensure the development of adequate therapeutic strategies. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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13 pages, 898 KiB  
Review
Exploring Mammalian Genome within Phase-Separated Nuclear Bodies: Experimental Methods and Implications for Gene Expression
by Annick Lesne, Marie-Odile Baudement, Cosette Rebouissou and Thierry Forné
Genes 2019, 10(12), 1049; https://doi.org/10.3390/genes10121049 - 17 Dec 2019
Cited by 13 | Viewed by 5719
Abstract
The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active/inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. [...] Read more.
The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active/inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase-separated nuclear bodies possibly contributes to mammalian genome organization and gene expression. Full article
(This article belongs to the Special Issue Disentangling Mechanisms of Genomic Regulation of Cell Functions at the Gene Level)
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