Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization

Abstract

DNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery

“…Current findings suggest that the conversion of 5-mC to 5-hmC is associated with demethylation processes [43][44][45], regulation of gene expression [46], and changes in the chromatin structure [47]. In this way, 5-hmC methylation could be an epigenetic mechanism participating in disease development, although these outcomes are still under investigation [44,48].…”

“…In this way, 5-hmC methylation could be an epigenetic mechanism participating in disease development, although these outcomes are still under investigation [44,48]. Due to the large presence of 5-hmC in the brain [49], several studies have been conducted in neurological diseases [50,51].…”

Integrative analysis of methylome and transcriptome in human blood identifies extensive sex- and immune cell-specific differentially methylated regions

“…58 In general, the depletion of DNA methylation does not necessarily induce gene activation but rather renders a permissive state for activation. 59 Thus, it has been suggested that combined epigenetic marks, such as histone markers, chromatin state, and DNA methylation, might be better predictors for expression level than position of the CpG sites with respect to the gene. 57 A confounding factor in defining this relationship is the fact that assays based upon bisulfite conversion, such as Human-Methylation450 BeadChips, do not distinguish between 5hmC and 5mC.…”

“…55 5hmC is mostly depleted in CGIs, but found in the exons of gene bodies and highly enriched in distal regulatory elements, which include enhancers, insulators, p300-binding sites, and DHSs. [59][60][61] Thus, the observed enrichment of immune cell-specific DMGs in enhancer elements could at least in part include 5hmC sites. 59 Pathway analysis revealed similar biological pathways for negatively and positively correlated genes, indicating that the direction of correlation is not specific to a biological function.…”

“…[59][60][61] Thus, the observed enrichment of immune cell-specific DMGs in enhancer elements could at least in part include 5hmC sites. 59 Pathway analysis revealed similar biological pathways for negatively and positively correlated genes, indicating that the direction of correlation is not specific to a biological function. However, 2 pathways, the inflammatory response and cell death pathways, were specific to only one of the directions, suggesting that the regulatory mechanism of these pathways may be different.…”