DNA Methylation: Superior or Subordinate in the Epigenetic Hierarchy?

Abstract

Epigenetic modifications are heritable changes in gene expression not encoded by the DNA sequence. In the past decade, great strides have been made in characterizing epigenetic changes during normal development and in disease states like cancer. However, the epigenetic landscape has grown increasingly complicated, encompassing DNA methylation, the histone code, noncoding RNA, and nucleosome positioning, along with DNA sequence. As a stable repressive mark, DNA methylation, catalyzed by the DNA methyltransferases (DNMTs), is regarded as a key player in epigenetic silencing of transcription. DNA methylation may coordinately regulate the chromatin status via the interaction of DNMTs with other modifications and with components of the machinery mediating those marks. In this review, we will comprehensively examine the current understanding of the connections between DNA methylation and other epigenetic marks and discuss molecular mechanisms of transcriptional repression in development and in carcinogenesis.

Genetic Diversity, Epigenetic Reprogramming and Environmental Factors: Leading Directions in the Study of the Complex Human Diseases

“…(34)(35)(36) Most DNA methylation is essential for normal development, and it plays a very important role in a number of key processes, including genomic imprinting, X-chromosome inactivation, and suppression of repetitive element transcription and transposition. (37) DNA methylation can be affected by both inherited DNA sequence variation and a broad range of environmental factors, such as nutrition, exposure to toxic pollutants and social environment. (38)(39)(40)(41) The state of genome instability in connection with the violation of DNA methylation processes appears to be the fundamental basis for the manifestation and/or maintenance of the pathological process in carcinogenesis, atherosclerosis, autoimmune process.…”

Development of Enhanced Reduced Representation Bisulfite Sequencing Method for Single-cell Methylome Analysis

“…Among these, we focused on DNA methylation. DNA methylation plays important roles in development, tumor formation and other processes [10]. It becomes more stable after differentiation than in early embryo and primordial germ cells.…”

Quantitative DNA methylation analysis of paired box gene 1 and LIM homeobox transcription factor 1 α genes in cervical cancer

“…CIN often occurs in women aged 25-35 years (6) and the highest incidence of CC occurs at ~47 years of age (9), suggesting a slow evolution from precancerous lesions to CC. Additionally, HPV vaccination for the prevention of CC is offered in numerous regions around the world, but it is not widely applied in a number of countries, including mainland China (4,10). Finally, since the 1950s, due to the widespread use of cervical cytology screening, cervical precancerous and cancerous lesions may be identified and treated early, resulting in a significant decrease in the incidence, and mortality of CC (11,12).…”

“…DNA methylation involves intensive epigenetic modifications that serve important roles in gene expression or silencing in normal mammalian cells (10,23). DNA methylation-induced alteration of C-phosphate-G (CpG) islands in tumor suppressor gene promoter regions is often observed in human cancer (24)(25)(26)(27).…”