Box 2 | Constitutive versus facultative heterochromatin

From the following article:

The role of nuclear architecture in genomic instability and ageing

Philipp Oberdoerffer & David A. Sinclair

Nature Reviews Molecular Cell Biology 8, 692-702 (September 2007)

doi:10.1038/nrm2238

There are two types of heterochromatin: constitutive and facultative (inducible). Although both types can be stably inherited over numerous cell divisions, each type has a distinct make-up and function. Constitutive heterochromatin mainly comprises repetitive genetic elements, such as telomeres and centromeres, that localize to the nuclear periphery. By contrast, facultative heterochromatin can form anywhere in the nucleus and its formation is required for mating-type gene silencing in budding yeast, and X-chromosome inactivation and developmental progression in mammalian cells (reviewed in Ref. 77).

Both constitutive and facultative heterochromatin form repressive chromatin structures and are associated with transcriptional silencing. Silencing by constitutive heterochromatin is considered to be indirect and rather unspecific in nature. Constitutive heterochromatin is thought to act primarily as a genome stabilizer that prevents gene rearrangements between highly similar genetic sequences and ensures efficient chromosomal segregation. As a by-product, genes that are adjacent to repetitive DNA can be silenced by the spreading of silent heterochromatin into non-repetitive, gene-containing regions — this phenomenon is known as position-effect variegation78.

Facultative heterochromatin is often localized to promoters and is established either in a developmentally regulated manner or in response to environmental triggers. It ensures the epigenetic silencing of genes in a certain cell type or tissue, and is an important mechanism for developmental programming and cell fate. Initiation of this form of heterochromatin depends on site-specific transcriptional repressors, which, in turn, recruit a silencing complex that contains histone-modifying enzymes and other structural proteins that maintain a silent state. Stress-induced facultative heterochromatin can be the consequence of cellular stress such as the induction of senescence. Its formation requires nuclear factors that are involved in cell-cycle progression and, possibly, the recruitment of the DNA-repair machinery12, 42.