DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics

Abstract

Epigenetics deals with the interactions between genes and the immediate cellular environment. These interactions go a long way in shaping up each and every person's individuality. Further, reversibility of epigenetic interactions may offer a dynamic control over the expression of various critical genes. Thus, tweaking the epigenetic machinery may help cause or cure diseases, especially cancer. Therefore, cancer epigenetics, especially at a molecular level, needs to be scrutinised closely, as it could potentially serve as the future pharmaceutical goldmine against neoplastic diseases. However, in view of its rapidly enlarging scope of application, it has become difficult to keep abreast of scientific information coming out of various epigenetic studies directed against cancer. Using this review, we have attempted to shed light on two of the most important mechanisms implicated in cancer, that is, DNA (deoxyribonucleic acid) methylation and histone modifications, and their place in cancer pathogenesis. Further, we have attempted to take stock of the new epigenetic drugs that have emerged onto the market as well as those in the pipeline that offer hope in mankind's fight against cancer.

Early-life DNA methylation profiles are indicative of age-related transcriptome changes

“…Epigenetic modifications, chromatin, and direct DNA modifications are key genomic regulatory processes required for proper development [1], gene imprinting [2–4], X chromosome inactivation [5–7], gene expression regulation [8], and genomic organization [9–11]. Disruptions to the epigenome can alter basic cellular regulation leading to a wide range of dysfunctional molecular programs [10–12].…”

Early life DNA methylation profiles are indicative of age-related transcriptome changes

“…DNA methylation can play multiple roles in regulating gene transcription by altering protein binding occupancy [64], regulation of alternative splicing [65][66][67][68][69], and through interactions with histone marks [70,11]. To examine DNA methylation patterns between genes differentially expressed during aging and those that remain unaltered, correlations between fold mRNA change with aging and gene body methylation levels (mean methylation from TSS to TES) ( Figure 3A,B) in early and late life were performed.…”

“…Epigenetic modifications, chromatin and direct DNA modifications, are key genomic regulatory processes required for proper development [1], gene imprinting [2][3][4], X chromosome inactivation [5][6][7], gene expression regulation [8], and genomic organization [9][10][11]. Disruptions to the epigenome can alter basic cellular regulation leading to a wide range of dysfunctional molecular programs [10][11][12].…”

“…Epigenetic modifications, chromatin and direct DNA modifications, are key genomic regulatory processes required for proper development [1], gene imprinting [2][3][4], X chromosome inactivation [5][6][7], gene expression regulation [8], and genomic organization [9][10][11]. Disruptions to the epigenome can alter basic cellular regulation leading to a wide range of dysfunctional molecular programs [10][11][12]. Impaired epigenetic control with aging has been proposed as an etiological factor common to age-related diseases ranging from diabetes to neurodegenerative diseases such as Alzheimer's disease [13][14][15][16][17][18].…”

Atypical Rho GTPases of the RhoBTB Subfamily: Roles in Vesicle Trafficking and Tumorigenesis

“…The promoter regions of all three RHOBTB genes have a high GC content with CpG islands. The hypermethylation of CpG islands results in the downregulation or complete abrogation of gene expression and is a frequent epigenetic alteration in primary tumors [ 34 ]. RHOBTB2 promoter methylation, normally a rare event, has been found increased and correlated to reduced or abolished expression of the gene in breast [ 25 , 35 , 36 ] and bladder [ 28 ] cancers.…”