Long-range heterochromatin repression and local transcriptional activation. (A) Establishment of heterochromatin involves removal of acetyl groups from histone tails (by HDAC), methylation of Lys 9 on histone H3 (H3K9me; by histone methyltransferase), and recruitment of chromodomain-containing proteins such as HP1. Heterochromatin is inherently processive, with the underlying cooperativity also accounting for its stability. Heterochromatin spreading can be blocked by transcriptionally active regions or insulators that may be associated with nuclear membrane and pore complexes. Nucleation and maintenance do not require sequence- specific DNA-binding proteins but are mediated by repetitive DNA sequences, RNAi machinery, or noncoding scaffold RNAs (such as Xist or HOTAIR). Some nuclear envelope/nuclear pore components appear to function as insulators. (B) Stimulus-induced transcriptional activation of a specific gene involves transcription factors whose recruitment is orchestrated by enhancers and promoters that contain clustered binding sites. In addition, these DNAbinding factors may need to be modified to allow for an exchange of corepressors (such as HDAC) with coactivators (such as HATs). Local acetylation of the histones of a single or a few nucleosomes may effect gene activation by affecting nucleosome compaction, recruiting additional coactivators, or components of the PIC, such as TAF1, which contains acetyl-lysine-binding bromodomains, or effecting conformational changes in a previously assembled PIC to allow for RNA Pol II recruitment, initiation, or release.