Fig. 5.

Regulatory chromatin markers and health- and disease-associated CpG methylation. A Chromatin in nondividing cells can be divided into euchromatin and heterochromatin, and the two chromatin states refer to areas that are transcriptionally active and inactive, respectively. Epigenetic factors include DNA/RNA methylation and histone modifications, RNA transcript variations (e.g., different splice forms of RNA as epigenetic regulators), and noncoding RNAs (ncRNAs, such as miRNAs, sRNAs, and ncRNAs as well as RNAi and AS), as well as chromatin architecture remodeling [150, 157–166]. Covalent epigenetic modifications of histones and DNA are the most common epigenetic marks, and they alter neighboring nucleosomes to impact the accessibility of loci for transcription factors and coregulators. The gene or regulatory element associated with these epigenetic modification marks indicates the status (active, repressive or poised). These epigenetic marks can be determined using epigenetic analyses. Examples include chromatin immunoprecipitation (ChIP), micrococcal nuclease (MNase) and DNase I hypernasality site (DHS) assays with PCR or sequencing techniques [152, 161, 162, 169–174]. B Heatmap showing the differentially methylated chemokine genes associated with health and disease. C Chemokine genes with differential CpG methylation associated with normal processes such as aging, body weight control, immune responses, metabolism and diseases such as neurological and mental disorders. D Health- and disease-associated CpG methylation is found in the CCR5/CCR2 gene cluster