Biological Methylation in Development and Cancer

A special issue of Epigenomes (ISSN 2075-4655).

Deadline for manuscript submissions: closed (31 May 2017) | Viewed by 41716

Special Issue Editors

Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, NY 10029, USA
Interests: methyltransferases; transcription; splicing; cancer; genomics
Special Issues, Collections and Topics in MDPI journals
Department of Basic Sciences, Faculty of Medicine and Health Sciences, Universidad Internacional de Cataluña (UIC), Carrer de Josep Trueta, 08017 Barcelona, Spain
Interests: epigenetics; gene expression; DNA methylation; cancer; genetic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past few years epigenetic studies have changed the way we see cell reprogramming and differentiation. Now we know that there is no need for the existence of a DNA mutation to change the fate of a cell, and that epigenetic changes at the chromatin level can be sufficient. Of all the possible epigenetic modifications Methylation has historically been considered one of the most stable marks. This view however has changed radically with the discovery of mechanisms that allow the removal of methyl marks from DNA, RNA and proteins.

Importantly while DNA methyltransferases inhibitors have long been tested in patients, more recently protein methyltransferases have also proven to be druggable enzymes, and selective and potent inhibitors have recently entered clinical trials, with great promise for targeted cancer therapy.

This special issue will be focused around epigenetic changes conducted by methyltransferases and demethylases and how these changes at the DNA or protein level regulate normal development or lead to cancerous transformation. We will consider Research or Methods manuscripts of exceptional interest on the following topics:

  • Effect of methyltransferases and demethylases implicated in development of any model organism.
  • Effect of methyltransferases and demethylases implicated in cancer.
  • Development of novel small molecule inhibitors of methyltransferases and demethylases.
  • Clinical studies investigating the role of methyltransferases and demethylases in cancer

Prof. Dr. Ernesto Guccione
Dr. Gaetano Verde
Guest Editors

Don’t miss out the deadline for submissions: 31 January 2017.

Please use the online submission system and select the Special Issue “Biological Methylation in Development and Cancer”.
If you would like to enquire about suitability of your article to this Special Issue please email your pre-submission enquiry to Professor Ernesto Guccione and Dr. Gaetano Verde with cc to

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Epigenomes is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • Epigenetics
  • Methyltransferases
  • Demethylases
  • DNA or Protein Methylation in Cancer
  • DNA or Protein Methylation in development

Published Papers (6 papers)

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Editorial

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6 pages, 207 KiB  
Editorial
5-Methylcytosine and 5-Hydroxymethylcytosine Signatures Underlying Pediatric Cancers
Epigenomes 2019, 3(2), 9; https://doi.org/10.3390/epigenomes3020009 - 09 May 2019
Cited by 1 | Viewed by 3675
Abstract
In addition to the genetic variations, recent evidence has shown that DNA methylation of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) underlies the pathogenesis of pediatric cancer. Given the high mortality rate, there is an urgent need to study the mechanisms contributing to the [...] Read more.
In addition to the genetic variations, recent evidence has shown that DNA methylation of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) underlies the pathogenesis of pediatric cancer. Given the high mortality rate, there is an urgent need to study the mechanisms contributing to the pathogenicity of pediatric cancer. Over the past decades, next-generation sequencing (NGS) has enabled us to perform genome-wide screening to study the complex regulatory mechanisms of 5mC and 5hmC underlying pediatric tumorigenesis. To shed light on recent developments on pediatric cancer predisposition and tumor progression, here we discuss the role of both genome-wide and locus-specific dysregulation of 5mC and 5hmC in hematopoiesis malignancy and neuroblastoma, the most common types of pediatric cancer, together with their therapeutic potential. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)

Research

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4187 KiB  
Article
Mining Novel Candidate Imprinted Genes Using Genome-Wide Methylation Screening and Literature Review
Epigenomes 2017, 1(2), 13; https://doi.org/10.3390/epigenomes1020013 - 13 Sep 2017
Cited by 3 | Viewed by 5802
Abstract
Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, [...] Read more.
Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered ~30% of the known human imprinted genes, and a further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherin cluster on 5q31.3; in mice, protocadherin genes have non-imprinted random monoallelic expression, which might also be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL, and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears to be a useful approach to reveal candidate imprinted genes. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
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2816 KiB  
Article
Helicase Lymphoid-Specific Enzyme Contributes to the Maintenance of Methylation of SST1 Pericentromeric Repeats That Are Frequently Demethylated in Colon Cancer and Associate with Genomic Damage
Epigenomes 2017, 1(1), 2; https://doi.org/10.3390/epigenomes1010002 - 22 Sep 2016
Cited by 17 | Viewed by 7420
Abstract
DNA hypomethylation at repetitive elements accounts for the genome-wide DNA hypomethylation common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) in several cancers, including 28 of 128 (22%) [...] Read more.
DNA hypomethylation at repetitive elements accounts for the genome-wide DNA hypomethylation common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) in several cancers, including 28 of 128 (22%) CRCs. SST1 somatic demethylation associated with genome damage, especially in tumors with wild-type TP53. Seven percent of the 128 CRCs exhibited a higher (“severe”) level of demethylation (≥10%) that co-occurred with TP53 mutations. SST1 demethylation correlated with distinct histone marks in CRC cell lines and primary tumors: demethylated SST1 associated with high levels of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark and lower levels of histone 3 lysine 9 trimethylation (H3K9me3). Furthermore, induced demethylation of SST1 by 5-aza-dC led to increased H3K27me3 and reduced H3K9me3. Thus, in some CRCs, SST1 demethylation reflects an epigenetic reprogramming associated with changes in chromatin structure that may affect chromosomal integrity. The chromatin remodeler factor, the helicase lymphoid-specific (HELLS) enzyme, called the “epigenetic guardian of repetitive elements”, interacted with SST1 as shown by chromatin immunoprecipitation, and down-regulation of HELLS by shRNA resulted in demethylation of SST1 in vitro. Altogether these results suggest that HELLS contributes to SST1 methylation maintenance. Alterations in HELLS recruitment and function could contribute to the somatic demethylation of SST1 repeat elements undergone before and/or during CRC pathogenesis. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
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Review

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22 pages, 310 KiB  
Review
The Relevance of Gender in Tumor-Influencing Epigenetic Traits
Epigenomes 2019, 3(1), 6; https://doi.org/10.3390/epigenomes3010006 - 28 Jan 2019
Cited by 4 | Viewed by 4699
Abstract
Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor’s fine-tuning is given. Throughout the [...] Read more.
Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor’s fine-tuning is given. Throughout the last decade epigenetics has been featured in cancer research and it is now clear that the underlying mechanisms, especially DNA and histone modifications, are important regulators of carcinogenesis and tumor progression. Another key regulator, which is well known but has been neglected in scientific approaches as well as molecular diagnostics and, consequently, treatment conceptualization for a long time, is the subtle influence patient gender has on molecular processes. Naturally, this is greatly based on hormonal differences, but from an epigenetic point of view, the diverse susceptibility to stress and environmental influences is of prime interest. In this review we present the current view on which and how epigenetic modifications, emphasizing DNA methylation, regulate various tumor diseases. It is our aim to elucidate gender and epigenetics and their interconnectedness, which will contribute to understanding of the prospect molecular orchestration of cancer in individual tumors. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
2696 KiB  
Review
Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis
Epigenomes 2017, 1(1), 4; https://doi.org/10.3390/epigenomes1010004 - 30 Mar 2017
Cited by 4 | Viewed by 9681
Abstract
Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of [...] Read more.
Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of lysine-specific demethylases—KDM1, Jumonji domain-containing demethylases, and lysyl oxidase-like 2 protein—has drastically changed this view, suggesting a role for dynamic histone methylation in different biological process. In this review, we describe the different mechanisms that these enzymes use to remove lysine histone methylation and discuss their role during physiological (cell differentiation) and pathological (carcinogenesis) processes. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
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287 KiB  
Review
New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know
Epigenomes 2017, 1(1), 3; https://doi.org/10.3390/epigenomes1010003 - 30 Jan 2017
Cited by 6 | Viewed by 9839
Abstract
Skin cancer is one of the most common neoplasms worldwide, with a surprising tendency to increase its incidence. As with many cancer types nowadays, early diagnosis and proper management carries an excellent prognosis, up to 5-year survival rate of above 95% for most [...] Read more.
Skin cancer is one of the most common neoplasms worldwide, with a surprising tendency to increase its incidence. As with many cancer types nowadays, early diagnosis and proper management carries an excellent prognosis, up to 5-year survival rate of above 95% for most skin cancers, even though the long-term survival rate among metastatic melanoma patients remains only 5%. This review aims to summarize recent discoveries in epigenetic changes connected with cutaneous malignant melanoma (CMM), comprising of DNA methylation, histone modifications, miRNA regulation, nucleosome positioning and chromatin remodelling. Undoubtedly, personalised medicine based on both genetic and epigenetic changes of cancer is the future, the question remains: how long will it take to transport this treatment from the bench to the bedside? Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
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