Fig 1

In a Giemsa-stained chromosome (left) the unstained regions (white) represent regions, which are thought to be less compact and transcriptionally active (euchromatin), and heavily stained regions (black) are considered transcriptionally inactive and highly condensed (heterochromatin). These observations have been reinforced by studies that demonstrated transcriptionally active euchromatin domains to be highly acetylated when compared to transcriptionally silenced chromosomal regions, which are hypoacetylated (9–12, 228–230). Electrostatic interactions between DNA (negatively charged) and N-terminal histone protein tails (which positively charged when deacetylated and loose their positive charge through acetylation) may at least in part serve as an explanation for the highly complex mechanisms that are involved in chromatin compaction. MeCP2, which recognizes methylated DNA, recruits HDACs, which are part of multisubunit repressor complexes (e.g., SIN3a or N-COR/SMRT-SIN3a) and mediates silencing of methylated DNA through deacetylation (15–17). Under such conditions chromosomal DNA is inaccessible to DNA-binding factors, which are necessary for transcription, repair, replication, etc. Conversely, demethylation and/or hyperacetylation are associated with transcriptional activation and the unfolding of chromatin, thereby allowing access to transcription factors and other regulators (231–233).