Higher-order folding of heterochromatin: protein bridges span the nucleosome arrays

In interphase eukaryotic nuclei, chromatin is divided into two morphologically distinct types known as heterochromatin and euchromatin. It has been long suggested that the two types of chromatin differ at the level of higher-order folding. Recent studies have revealed the features of chromatin 3D architecture that distinguish the higher-order folding of repressed and active chromatin and have identified chromosomal proteins and their modifications associated with these structural transitions. This review discusses the molecular and structural determinants of chromatin higher-order folding in relation to mechanism(s) of heterochromatin formation and genetic silencing during cell differentiation and tissue development.