Figure 2.

Selected Mendelian disorders of the histone machinery caused by alterations of writers (highlighters) and erasers. Acetylation is a binary mark (present or not), and histone lysine methylation is a quaternary mark (mono-, di-, tri-, or unmethylated). The diagram illustrates these two types of modifications (see key) on two of the N-terminal histone tails, histone H3 and histone H4. The writers (highlighters) and erasers place and remove the modifications, respectively; some of these are associated with open, permissive chromatin (green), and others are associated with closed, repressive chromatin (red). Based on the enzymatic component of the epigenetic machinery involved and the predicted consequence of the reported mutations for each disorder, the diagram shows conditions that would be expected to shift the balance toward closed chromatin states at target loci (top) and those that would be expected to shift the balance toward open chromatin states at target loci (bottom). The former category includes Rubinstein–Taybi syndrome (RTS) (93, 101), Kabuki syndrome (KS) (71, 86), Wiedemann–Steiner syndrome (WSS) (61), and possibly Weaver syndrome (WS) and Sotos syndrome (SS) (41, 69, 116); the latter category includes brachydactyly–mental retardation (BDMR) syndrome (128), Kleefstra syndrome (KLFS) (66), Claes–Jensen syndrome (CJS) (60), and possibly Sotos syndrome (SS) (69). For EZH2 in WS and NSD1 in SS (marked with asterisks), the epigenetic consequences are currently unclear.