Chromosomal requirements for formation of multivalent human nucleoli

Abstract

Human nucleoli are multivalent, involving contributions from up to 10 NOR-bearing acrocentric chromosome p-arms. Precision megabase-scale chromosome engineering defines the requirements for this major genome organizational event. NOR deletions reveal that p-arm clustering can occur independent of rDNA. Deletion of all NOR-distal or NOR-proximal sequences individually have only a marginal effect on nucleolar association. Finally, deletion of an entire p-arm, while leaving centromere function intact, destroys the nucleolar association potential of that acrocentric. We propose that formation of multivalent nucleoli is not a nucleolar fusion event per se; rather it is driven by the surrounding chromosomal context of NORs.