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Epigenomics and Epitranscriptomics Crosstalk
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Epigenomics and Epitranscriptomics Crosstalk

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

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 21361

Special Issue Editors

Dr. María Gomez

E-Mail Website
Guest Editor
Genome Dynamics and Function Unit, Centro de Biología Molecular Severo Ochoa, Spanish Research Council (CSIC)/Madrid Autonomous University (UAM), 28049 Madrid, Spain
Interests: genome biology; DNA replication; chromatin; epigenetics; transcription
Dr. Sandra Blanco Benavente

E-Mail Website
Co-Guest Editor
Centro de Investigación del Cáncer (CSIC/USAL), Campus Universitario Miguel de Unamuno s/n, 37007-Salamanca, Spain
Interests: cancer epitranscriptomics; neurodegeneration; rare diseases; RNA methylation

Special Issue Information

Dear Colleagues,

Epigenomic (modifications of the DNA and histones) and epitranscriptomic (modifications of the RNA) information shape the genome output, giving rise to the gene activity states that specify cell identity. Both epimodifications are dynamic, harboring the potential to change in response to regulatory cues as well as to external stimuli and environmental influences, such as nutrients or stress. They also slowly change from development to aged organisms. In fact, the involvement of epigenetic and epitranscriptomic dysregulation in a great number of diseases is steadily increasing, highlighting their major impact in virtually all fields of life and health science. Both types of marks are specifically deposited, removed, and decoded by a repertoire of enzymes, so far better characterized in the case of DNA and histones, although the RNA modification field is rapidly catching up. A better understanding of the mechanisms and functions of RNA modifications, the combinations of marks on different RNA biotypes, and the potential crosstalk between epigenomic and epitranscriptomic marks is essential to fully unravel the complexity of these multifaceted regulatory mechanisms of gene expression. Recent developments, future perspectives, and challenges integrating these convergent research fields are the topic of this Special Issue in Genes on “Epigenomics and Epitranscriptomics Crosstalk”.

Dr. María Gomez
Dr. Sandra Blanco Benavente
Guest Editors

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Keywords

  • DNA methylation
  • chromatin variants and histone marks
  • epigenome
  • epitranscriptome
  • RNA modifications
  • epidrugs

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Published Papers (5 papers)

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Research

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12 pages, 752 KiB  
Article
Slow RNAPII Transcription Elongation Rate, Low Levels of RNAPII Pausing, and Elevated Histone H1 Content at Promoters Associate with Higher m6A Deposition on Nascent mRNAs
by Alicia Gallego, José Miguel Fernández-Justel, Sara Martín-Vírgala, Magdalena M. Maslon and María Gómez
Genes 2022, 13(9), 1652; https://doi.org/10.3390/genes13091652 - 14 Sep 2022
Cited by 2 | Viewed by 2886
Abstract
N6-methyladenosine modification (m6A) fine-tunes RNA fate in a variety of ways, thus regulating multiple fundamental biological processes. m6A writers bind to chromatin and interact with RNA polymerase II (RNAPII) during transcription. To evaluate how the dynamics of the transcription process impact m6A deposition, [...] Read more.
N6-methyladenosine modification (m6A) fine-tunes RNA fate in a variety of ways, thus regulating multiple fundamental biological processes. m6A writers bind to chromatin and interact with RNA polymerase II (RNAPII) during transcription. To evaluate how the dynamics of the transcription process impact m6A deposition, we studied RNAPII elongation rates in mouse embryonic stem cells with altered chromatin configurations, due to reductions in linker histone H1 content. We found that genes transcribed at slow speed are preferentially methylated and display unique signatures at their promoter region, namely high levels of histone H1, together with marks of bivalent chromatin and low RNAPII pausing. They are also highly susceptible to m6A loss upon histone H1 reduction. These results indicate that RNAPII velocity links chromatin structure and the deposition of m6A, highlighting the intricate relationship between different regulatory layers on nascent mRNA molecules. Full article
(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)
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Review

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18 pages, 1315 KiB  
Review
The Role of the m6A RNA Methyltransferase METTL16 in Gene Expression and SAM Homeostasis
by Jacqueline E. Mermoud
Genes 2022, 13(12), 2312; https://doi.org/10.3390/genes13122312 - 8 Dec 2022
Cited by 4 | Viewed by 3609
Abstract
The RNA methylation of adenosine at the N6-position (m6A) has attracted significant attention because of its abundance and dynamic nature. It accounts for more than 80% of all RNA modifications present in bacteria and eukaryotes and regulates crucial aspects of RNA [...] Read more.
The RNA methylation of adenosine at the N6-position (m6A) has attracted significant attention because of its abundance and dynamic nature. It accounts for more than 80% of all RNA modifications present in bacteria and eukaryotes and regulates crucial aspects of RNA biology and gene expression in numerous biological processes. The majority of m6A found in mammals is deposited by a multicomponent complex formed between methyltransferase-like (METTL) proteins METTL3 and METTL14. In the last few years, the list of m6A writers has grown, resulting in an expansion of our understanding of the importance of m6A and the methylation machinery. The characterization of the less familiar family member METTL16 has uncovered a new function of the m6A methylation apparatus, namely the fine-tuning of the cellular levels of the major methyl donor S-adenosylmethionine (SAM). METTL16 achieves this by adjusting the levels of the enzyme that synthesizes SAM in direct response to fluctuations in the SAM availability. This review summarizes recent progress made in understanding how METTL16 can sense and relay metabolic information and considers the wider implications. A brief survey highlights similarities and differences between METTL16 and the better-known METTL3/14 complex, followed by a discussion of the target specificity, modes of action and potential roles of METTL16. Full article
(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)
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17 pages, 965 KiB  
Review
Epigenetic and Epitranscriptomic Gene Regulation in Plasmodium falciparum and How We Can Use It against Malaria
by Rafael Serrano-Durán, Diana López-Farfán and Elena Gómez-Díaz
Genes 2022, 13(10), 1734; https://doi.org/10.3390/genes13101734 - 27 Sep 2022
Cited by 8 | Viewed by 4150
Abstract
Malaria, caused by Plasmodium parasites, is still one of the biggest global health challenges. P. falciparum is the deadliest species to humans. In this review, we discuss how this parasite develops and adapts to the complex and heterogenous environments of its two hosts [...] Read more.
Malaria, caused by Plasmodium parasites, is still one of the biggest global health challenges. P. falciparum is the deadliest species to humans. In this review, we discuss how this parasite develops and adapts to the complex and heterogenous environments of its two hosts thanks to varied chromatin-associated and epigenetic mechanisms. First, one small family of transcription factors, the ApiAP2 proteins, functions as master regulators of spatio-temporal patterns of gene expression through the parasite life cycle. In addition, chromatin plasticity determines variable parasite cell phenotypes that link to parasite growth, virulence and transmission, enabling parasite adaptation within host conditions. In recent years, epitranscriptomics is emerging as a new regulatory layer of gene expression. We present evidence of the variety of tRNA and mRNA modifications that are being characterized in Plasmodium spp., and the dynamic changes in their abundance during parasite development and cell fate. We end up outlining that new biological systems, like the mosquito model, to decipher the unknowns about epigenetic mechanisms in vivo; and novel methodologies, to study the function of RNA modifications; are needed to discover the Achilles heel of the parasite. With this new knowledge, future strategies manipulating the epigenetics and epitranscriptomic machinery of the parasite have the potential of providing new weapons against malaria. Full article
(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)
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24 pages, 1188 KiB  
Review
Epigenetic and Epitranscriptomic Control in Prostate Cancer
by Judith López, Ana M. Añazco-Guenkova, Óscar Monteagudo-García and Sandra Blanco
Genes 2022, 13(2), 378; https://doi.org/10.3390/genes13020378 - 18 Feb 2022
Cited by 18 | Viewed by 4969
Abstract
The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key [...] Read more.
The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key players in tumorigenesis. In this review we summarize the molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer. Full article
(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)
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15 pages, 1104 KiB  
Review
Driving Chromatin Organisation through N6-methyladenosine Modification of RNA: What Do We Know and What Lies Ahead?
by Tommaso Selmi and Chiara Lanzuolo
Genes 2022, 13(2), 340; https://doi.org/10.3390/genes13020340 - 12 Feb 2022
Cited by 9 | Viewed by 4159
Abstract
In recent years, there has been an increase in research efforts surrounding RNA modification thanks to key breakthroughs in NGS-based whole transcriptome mapping methods. More than 100 modifications have been reported in RNAs, and some have been mapped at single-nucleotide resolution in the [...] Read more.
In recent years, there has been an increase in research efforts surrounding RNA modification thanks to key breakthroughs in NGS-based whole transcriptome mapping methods. More than 100 modifications have been reported in RNAs, and some have been mapped at single-nucleotide resolution in the mammalian transcriptome. This has opened new research avenues in fields such as neurobiology, developmental biology, and oncology, among others. To date, we know that the RNA modification machinery finely tunes many diverse mechanisms involved in RNA processing and translation to regulate gene expression. However, it appears obvious to the research community that we have only just begun the process of understanding the several functions of the dynamic web of RNA modification, or the “epitranscriptome”. To expand the data generated so far, recently published studies revealed a dual role for N6-methyladenosine (m6A), the most abundant mRNA modification, in driving both chromatin dynamics and transcriptional output. These studies showed that the m6A-modified, chromatin-associated RNAs could act as molecular docks, recruiting histone modification proteins and thus contributing to the regulation of local chromatin structure. Here, we review these latest exciting findings and outline outstanding research questions whose answers will help to elucidate the biological relevance of the m6A modification of chromatin-associated RNAs in mammalian cells. Full article
(This article belongs to the Special Issue Epigenomics and Epitranscriptomics Crosstalk)
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