5.11: Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
Difference between euchromatin and heterochromatin
Euchromatin is a lightly stained, gene-rich, and loosely-bound chromatin region. It is usually dispersed in the nucleus. The histones of euchromatin are extensively acetylated, which allows loose chromatin compaction.
In contrast, heterochromatin is a darkly stained, repeat-rich, gene-poor, and compact chromatin. It is mostly seen at the nuclear periphery, often as clumps. The histones of heterochromatin are methylated, which enables a compact chromatin structure.
Chromosomal rearrangements may position euchromatin genes next to heterochromatin. Such gene rearrangements can result in gene silencing by virtue of being placed near heterochromatin, rather than a change in the gene itself. This phenomenon is called "position-effect variegation (PEV)." Hence, the juxtaposed gene becomes silent in some cells where it is normally active, resulting in a variegated phenotype. The phenomenon of PEV is well studied in Drosophila.
The formation of heterochromatin depends on the histone H3 methylation followed by the association with nonhistone proteins such as Heterochromatin Protein 1 or HP1. Usually, heterochromatin and euchromatin are separated by a buffer region with many repeat-rich regions. PEV indicates that heterochromatin, once formed, can spread beyond the buffer region into the adjoining chromatin. In humans, HUSH complex methylates histones and contributes to the spreading of heterochromatin and hence, position effect variegation.