Chromosomal condensation leads to a preference for peripheral heterochromatin

Abstract

A layer of dense heterochromatin is found at the periphery of the nucleus. Because this peripheral heterochromatin functions as a repressive phase, mechanisms that relocate genes to the periphery play an important role in regulating transcription. Using Monte-Carlo simulations, we show that an interaction between chromatin and the nuclear boundary need not be specific to heterochromatin in order to preferentially locate heterochromatin to the nuclear periphery. This observation considerably broadens the class of possible interactions that result in peripheral positioning to include boundary interactions that either weakly attract all chromatin or strongly bind to a randomly chosen small subset of loci. The key distinguishing feature of heterochromatin is its high chromatin density with respect to euchromatin. In our model this densification is caused by HP1s preferential binding to H3K9me3 marked histone tails. We conclude that factors that are themselves unrelated to the nuclear periphery can determine which genomic regions condense to form heterochromatin and thereby control which regions are relocated to the periphery.