Illustration of the nuclear distribution of histone modifications and their association with heterochromatin protein 1 (HP1) proteins, centromeres, telomeres, and both active and inactive X chromosomes in normal (untreated) cells (A,C) and in cells treated with histone deacetylase inhibitor (TSA) (B,D). (A) Epigenetic profiles of centromeres, telomeres, and X chromosomes in the untreated cell. Because of technical restrictions, only one example of H3K9me2 is shown in a centromeric region (under no. 10). For the same reasons, only one telomeric region is illustrated in A (under nos. 1 and 5). (B) Nuclear redistribution of centromeric clusters and HP1 proteins in cells treated with TSA. Epigenetic modifications, as documented in A, were not tested after HDACI in any of the publications used in the references. (C) Nuclear distribution of H3K9 acetylation, H3K9 dimethylation, and H3K4 dimethylation in untreated cells. (D) Nuclear distribution of H3K9 acetylation, H3K9 dimethylation, and H3K4 dimethylation in a TSA-treated cell. This illustration was made on the basis of results published by the following authors: (1) Barbin et al. (1994); (2) Bártová et al. (2005); (3) Bártová et al. (2007); (4) Csankovszki et al. (2001); (5) García-Cao et al. (2004); (6) Gilchrist et al. (2004); (7) Khalil and Driscoll (2006); (8) Kohlmaier et al. (2004); (9) Kourmouli et al. (2004); (10) summarized by Lachner et al. (2003); (11) Lehnertz et al. (2003); (12) Minc et al. (1999,2000,2001); (13) Rougeulle et al. (2004); (14) e.g., Skalníková et al. (2007) and Keohane et al. (1996); (15) Taddei et al. (2001).

Model of formation of transcriptionally active and inactive chromatin by histone modifications. The scheme of the three core nucleosomes is used to describe chromatin. The acetyl group, especially on H3K9, and the methyl group on H3K4 associate with the transcriptionally active chromatin state of the mammalian genome. Histone acetylation is initiated by histone acetyl transferases (HATs; such as GNAT, MYST, and CBP/p300) and removed by histone deacetylases (HDACs; classes I, II, III). H3K4 methylation is induced by specific histone methylases, such as hSET1A, and removed by histone demethylase LSD1, which leads to activation of the HMT such as Suv39H1, which mediates H3K9 methylation. The chromodomain of the HP1 protein can recognize methylated H3K9, resulting in the propagation of transcriptionally silent chromatin. In euchromatic loci, this process is additionally mediated by co-repressors, such as retinoblastoma protein pRb, and constitutive heterochromatin is stabilized by HP1 binding to regional H3K9 methylation, which also involves incorporation of RNA (summarized by Lachner and Jenuwein 2002). Subsequently DNA methyltransferases (DNMTs) are activated, leading to DNA methylation. Methylated DNA is recognized by methyl-DNA-binding proteins, such as MeCP2, which, in turn, can associate with HDAC activity to eliminate the rest of the acetylated histones. Therefore, DNA methylation can facilitate additional histone methylation to enhance the repressed state of chromatin.