Polymeric nature of tandemly repeated genes enhances assembly of constitutive heterochromatin in fission yeast

Heterochromatin has been thought to be assembled by phase separation of chromatin. However, a fission yeast has only three chromosomes and the heterochromatin of this organism is not likely to be assembled by phase separation, which is a collective phenomenon of many chains. Motivated by our recent experiments that demonstrate that the tandemly repeated genes become heterochromatin, we constructed a theory of heterochromatin assembly by taking into account the connectivity of these genes along the chromatin in the kinetic equations of small RNA production and histone methylation, which are the key biochemical reactions involved in the heterochromatin assembly. Our theory predicts that the polymeric nature of the tandemly repeated genes ensures the steady production of small RNAs because of the stable binding of nascent RNAs produced from the genes to RDRC/Dicers at the surface of nuclear membrane. This theory also predicts that the compaction of the tandemly repeated genes suppresses the production of small RNAs, consistent with our recent experiments. This theory can be extended to the small RNA-dependent gene silencing in higher organisms.