Practice question

Histone octamer assembly follows ordered hierarchical pathway in vitro and via chaperones in vivo. H3 and H4 first form heterodimer via histone fold helices interaction, two dimers associate via H3-H3 four-helix bundle to form stable H3-H4 tetramer (H3-H4)2. This tetramer binds DNA first during replication-coupled assembly, serving as kernel onto which two H2A-H2B dimers deposit to complete octamer. H2A-H2B alone cannot tetramerize; H1 associates externally after nucleosome formation. Conservation of tetramer during replication ensures epigenetic inheritance of H3-H4 modifications to daughter strands, maintaining heterochromatin memory.