An epigenetic view of developmental diseases: new targets, new therapies

Xie, Pei; Zang, Liqun; Li, Xuekun; Shu, Qiang

doi:10.1007/s12519-016-0020-3

Cited by 21 publications

(17 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, the key principles of the methylation pathways, in terms of location and regulation of DNA templated processes, are highly conserved throughout mammals. Indeed, their importance is underscored by the fact that disruption of these processes, through inherited or acquired mutations in the main protagonists, results in embryonic lethality or can produce severe disease states [1][2][3][4][5] . Mutations related to developmental diseases have been well described in the literature and the major mutational targets are listed in Supplementary Table 1.…”

Section: [H1] Methylation In Ageing and Cancermentioning

confidence: 99%

See 1 more Smart Citation

The roles of DNA, RNA and histone methylation in ageing and cancer

Michalak

Burr

Bannister

et al. 2019

Nat Rev Mol Cell Biol

416

321

View full text Add to dashboard Cite

Chromatin is a macromolecular complex predominantly comprising DNA, histones and RNA. Its methylation is highly conserved throughout phylogeny as it provides an instructive template that helps coordinate context dependent access for gene expression, DNA repair and DNA replication. Dynamic changes in chromatin methylation are central to cell fate determination and normal development of the organism. Consequently, inherited or acquired mutations in the major epigenetic protagonists that regulate methylation of DNA, RNA and/or histone proteins are commonly observed in developmental disorders, ageing and cancer. This has provided the impetus for the clinical development of epigenetic therapies aimed to reset the methylation imbalance observed in these conditions. In this review we discuss the key principles of chromatin methylation and focus on how this fundamental biological process is corrupted in cancer. We discuss methylation-based cancer therapies and provide a perspective on the emerging data from early phase clinical trials therapies that target regulators of DNA and histone methylation. We also highlight promising future strategies, including monitoring chromatin methylation for diagnostic purposes and combination epigenetic therapy strategies that may improve immune surveillance in cancer and increase the efficacy of conventional and targeted anti-cancer drugs.

show abstract

Section: [H1] Methylation In Ageing and Cancermentioning

confidence: 99%

“…They co-operate with dedicated "erasers" and "readers" -the protein machinery that removes or recognizes these methylation marks. The importance of the various methylation pathways is highlighted by the fact that their dysregulation is linked to many diseases [1][2][3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

The roles of DNA, RNA and histone methylation in ageing and cancer

Michalak

Burr

Bannister

et al. 2019

Nat Rev Mol Cell Biol

416

321

View full text Add to dashboard Cite

show abstract

“…Lastly, NSun2 mRNA forms an in vivo complex with the TDP-43-associated protein, FUS, indicating the presence of a complex mechanism involving different RNA metabolism pathways [118]. The potential role of m 6 A residues in dendritic localization and stability of ASD associated mRNAs have been recently reviewed [119]. Although there is no direct evidence of m 6 A methylation affecting TDP-43/FMRP-regulated neuronal translation or neurological disorders, it should be noted that in human cells more than 12,000 m 6 A sites in about 7000 mRNAs have been identified [119] and the most of m 6 A RNA methylation found in the last exons.…”

Section: Potential Roles Of Rna Modifications In Tdp-43/fmrp-associatmentioning

confidence: 99%

“…The potential role of m 6 A residues in dendritic localization and stability of ASD associated mRNAs have been recently reviewed [119]. Although there is no direct evidence of m 6 A methylation affecting TDP-43/FMRP-regulated neuronal translation or neurological disorders, it should be noted that in human cells more than 12,000 m 6 A sites in about 7000 mRNAs have been identified [119] and the most of m 6 A RNA methylation found in the last exons. This might influence 3 -UTR-mediated translational regulation of mRNAs [120,121].…”

Section: Potential Roles Of Rna Modifications In Tdp-43/fmrp-associatmentioning

confidence: 99%

Epitranscriptome and FMRP Regulated mRNA Translation

2017

View full text Add to dashboard Cite

An important regulatory mechanism affecting mRNA translation involves various covalent modifications of RNA, which establish distinct epitranscriptomic signatures that actively influence various physiological processes. Dendritic translation in mammalian neurons is a potent target for RNA modification-based regulation. In this mini-review, we focus on the effect of potential RNA modifications on the spatiotemporal regulation of the dendritic translation of mRNAs, which are targeted by two important neuronal translational co-regulators, namely TDP-43 and Fragile X Mental Retardation Protein (FMRP).

show abstract

“…24 5-Hydroxymethylcytosine is also enriched in exons and near transcriptional start sites. 25 5-Hydroxmethylcytosine has been found to be especially abundant in the brain, particularly in Purkinje neurons. 26 Embryonic stem cells also exhibit elevated hmC levels.…”

mentioning

confidence: 99%

Methods for detection of cytosine and thymine modifications in DNA

Berney

McGouran

2018

Nat Rev Chem

View full text Add to dashboard Cite

Methylation of cytosine at the 5-position is a common epigenetic marker in mammalian DNA, and plays an important role in regulating gene expression. Oxidised derivatives of 5-methylcytosine have recently been discovered. As well as being intermediates in an active demethylation pathway, some of these oxidised derivatives may function as epigenetic markers in their own right. Oxidised derivatives of thymine are also known as products of DNA damage. There is evidence however that one such derivative, 5-hydroxymethyluracil, may play an epigenetic role. There is a pressing need to learn more about these modifications, due to the role epigenetic markers play in development, and diseases such as cancer. This emerging area of research requires methods for detecting cytosine and thymine modifications in DNA with a high degree of accuracy and sequence specificity. This review will introduce the biochemistry of cytosine and thymine modifications, and discuss new and established detection methods which have been developed to overcome the high degree of difficulty associated with studying these modifications in DNA. Introduction: Cytosine and Thymine Modifications DNA codes for all the proteins necessary for life, but the DNA sequence is not the sole determinant of all the phenotypic traits of cells and organisms. Transcription of DNA is tightly regulated by epigenetic modifications, which play an important role in controlling when and where specific genes are expressed. 1,2 Epigenetic modifications regulate important processes such as cellular differentiation, and are also implicated in various diseases including cancer, autism spectrum disorder, and other developmental diseases such as Rett syndrome. 3-5 Epigenetic control of gene expression is often mediated through covalent modification of DNA itself, or of the histone proteins which pack DNA in the nucleus. These modifications do not result in changes to the DNA sequence, but can affect the binding of certain proteins to the DNA, including transcription factors and proteins which regulate chromatin structure. 6-8 In mammals and many other eukaryotes, the most common epigenetic covalent modification of DNA is methylation of cytosine (C) at the 5-position. Such modifications can be inherited, but can also be enzymatically introduced and removed in response to stimuli. 9 5-Methylcytosine (mC) is introduced by the methylation of cytosine residues by DNA-methyltransferases (DNMTs) with an S-adenosylmethionine cofactor. 5-Methylcytosine is most often found in the context of 5'-cytosinephosphate-guanine-3' (CpG) dinucleotides. Regions containing a high density of CpG sequences are found in about 72% of promoters in the human genome. 10 Methylation of these regions causes

show abstract

An epigenetic view of developmental diseases: new targets, new therapies

Abstract: DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Cited by 21 publications

References 62 publications

The roles of DNA, RNA and histone methylation in ageing and cancer

The roles of DNA, RNA and histone methylation in ageing and cancer

Epitranscriptome and FMRP Regulated mRNA Translation

Methods for detection of cytosine and thymine modifications in DNA

Contact Info

Product

Resources

About