Cindy Boer

Epigenomics in bone and cartilage disease | 35 1.2 chromatin modifiers such as polycomb repressive complex proteins (PRC1 and PRC2) or activating chromatin modifiers[9]. Some lncRNAS are mainly located in the cytosol, where they target mRNAs and downregulate protein translation. Interestingly, they may also act as decoys for miRNAs, thus preventing the inhibitory effect of the binding of miRNAs to their target mRNAs[10]. Box 1: Epigenomics‐Related Terms • Chromatin: The complex of DNA and its packaging molecules. The core of the chromatin is the nucleosome, which consists of an octamer of 4 histones around which 147 bp of DNA is wrapped around. • Chromosome conformation capture and Hi‐C: Techniques used to map the spatial (3D) organization of the chromatin in the nucleus. Chromosome conformation capture (3C) quantifies the number of interactions between a given loci and the rest of the genome. In Hi‐C, all genomic interaction between all genomic regions are quantified. • CTCF : CCCTC‐binding factor, highly conserved zinc finger protein involved in diverse genomic regulatory functions, including transcriptional activation/repression, insulation, imprinting, and X‐chromosome inactivation, through mediating the formation of chromatin loops. • DNA methyl‐transferases (DNMTs) : Family of enzymes responsible for the methylation of DNA. DNMT1 recognizes hemimethylated CpG sites on newly replicated DNA and thus it maintains the methylation pattern through cell divisions. On the other hand, DNMT3A/3B are the novo methylases, capable of converting unmethylated CpGs into methylated CpGs in double‐strand DNA, which is particularly important during embryogenesis and cell differentiation. • Epigenetics: Mechanisms causing changes in gene expression that are heritable through cell divisions and do not include modifications of DNA sequence. • Epigenome‐wide association study (EWAS): Studies of the relationship between many epigenetic marks distributed throughout the genome and phenotypic characteristics. So far, most studies aimed to analyze DNA methylation. • Epigenomics: Usually refers to the epigenetic changes in many genes or even through the whole genome. • Genome‐wide association study (GWAS): Studies of the relationship between many genetic variants (usually hundred thousands or millions) distributed throughout the genome and phenotypic characteristics. • Histone code : Hundreds of different posttranslational modifications (PTMs) and their combinatorial patterns form a code, the histone code. This code can give rise to a prescribed transcriptional or other genomic regulatory response, interpreted by specialized proteins that can read, write, and erase histone PTMs. • Histone deacetylases (HDACs): Family of enzymes removing acetylation marks from histone tails. These epigenetic “erasers” are very important for modulating gene expression because histone acetylation is usually associated with active chromatin. • Long non‐coding RNAs (lncRNAs): ncRNAs with more than 200 nucleotides that regulate gene expression and interact with other epigenetic mechanisms. • Methylation quantitative trait loci (meQTL): A DNA locus (usually a single‐nucleotide polymorphism [SNP]) that is associated with DNA‐methylation levels from a certain CpG. • MicroRNAs (miRNAs): Small ncRNAs, 18 to 25 nucleotides long. One known function (of the many that are known) of miRNA’s target mRNAs, which interferes with protein translation. • Non‐coding RNAs (ncRNAs): RNAs that do not code proteins but have regulatory roles on chromatin structure, gene expression, or translation. There are multiple types, with different sizes and functions. • Quantitative trait loci (QTL): A DNA locus that is associated with a particular quantitative phenotypic trait. • Ten–eleven translocation (TET): Family of proteins involved in the demethylation of CpGs. • Topologically associated domain (TAD): Chromatin conformation capture techniques, such as Hi‐C, showed that the genome was divided in compartments that interact more frequently with themselves than the rest of the genome. Regulatory regions, such as enhancers, usually contact genes located within the same TAD as the regulatory region but not outside of their TAD.