Non-coding RNAs demystify constitutive heterochromatin as essential modulator of epigenotype

Abstract

Heterochromatin, ever since its discovery in 1928 as a distinct cytological entity showing differential condensation cycle than euchromatin, has remained enigmatic because of the general paucity of typical protein-coding genes and highly variable quantities in different genomes. While the significance of developmentally regulated facultative heterochromatin regions has been relatively better understood and appreciated, the repetitive and transposon sequence rich but protein-coding gene poor constitutive heterochromatin has continued to be a puzzle and ideas about its requirement for biological systems have varied from ‘junk’ or ‘selfish’ to very significant. Studies in recent decades on the diverse non-coding RNAs (ncRNAs) in eukaryotes have revealed them as essential parts of multi-layered regulatory networks. Interestingly, a significant contribution to the cellular ncRNAs pool seems to be derived from the constitutive heterochromatic regions and thus, as was suggested by several classical genetic studies, the constitutive heterochromatin can indeed have significant to subtle effects on activities of numerous other genes and, therefore, have far-reaching evolutionary consequences under natural conditions. This review briefly discusses, using examples mostly from Drosophila, the general organization of constitutive heterochromatin and how these regions can affect the spatial organization of chromatin in nucleus and how the diverse ncRNAs derived from such regions directly or indirectly modulate activities of many genes on other chromosomes. Interestingly, the diversity of small and large phenotypic effects that were empirically ascribed in classical studies to be associated with constitutive heterochromatin can now be understood through ncRNA metabolism. The functional and evolutionary significance of the heterochromatin is much more than it merely being a condensed and repressive state as a mechanism to keep the transposons etc. silent. The enigma of heterochromatin is to be viewed in light of the fact that biological systems are products of chance and necessity and, therefore, do not always follow the human reductionist logic.