Cindy Boer

36 | Chapter 1.2 ▲ Figure 1: Schematic overview of epigenetics : chromatin modifications and structure. (A) The DNA in the nucleus is present in the form of chromosomes. These inhabit distinct territories within the nucleus, allowing for the formation of distinct intra‐ or interchromosomal contacts. DNA methylation is the chemical addition of a methyl group to cytosines in DNA. The chromatin is organized in nucleo- somes made of DNA wrapped around an octamer of 4 histones (H2A, H2B, H3, and H4). Posttranslation- al modifications (PTM) of specific amino acids in the N‐terminal tail of histones, such as methylation, phosphorylation, acetylation, and ubiquitylation, remodel the shape and subsequently the function of the chromatin into repressive and active chromatin. Chromatin loops enable distant enhancers to come into close contact with their target gene promoters or create regions of gene silencing. The proteins CTCF and cohesin are known to be involved in the mediation of such chromatin loops. (B) Histone tails can contain many different or even multiple PTMs. This combination of PTMs, the histone code, confers meaning on the function or the state of that particular part of the chromatin. For several histone PTMs, their chromatin state is known, such as H3K4me1 for active enhancers and H3K4me3 for active promot- ers. (C) Chromatin conformation capture techniques, such as Hi‐C, have revealed the compartmental- ization of the genome into topologically associated domains (TADs), which are regions of preferential chromatin interactions. Depicted here is a stylistic interpretation of Hi‐C data, where the darker colored the bloc between two genomic regions, the more genomic interactions are quantified. Epigenomic interplay It is worth emphasizing that epigenetic mechanisms often act in concert by interacting with each other. For example, MeCP2, a protein recognizing methylated CpGs, promotes the activity of HDACs. On the other hand, some histone marks modulate the binding of