RT Journal Article
SR Electronic
T1 CDK-regulated phase separation seeded by histone genes ensures precise growth and function of Histone Locus Bodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 789933
DO 10.1101/789933
A1 Woonyung Hur
A1 Marco Tarzia
A1 Victoria E. Deneke
A1 Esteban A. Terzo
A1 Robert J. Duronio
A1 Stefano Di Talia
YR 2019
UL http://biorxiv.org/content/early/2019/10/02/789933.abstract
AB Many membrane-less organelles form through liquid-liquid phase separation, but how their size is controlled and whether size is linked to function remain poorly understood. The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of histone mRNAs. Here, we show that Drosophila HLBs form through phase separation of the scaffold protein multi-sex combs (Mxc). The size of HLBs is controlled in a precise and dynamic manner that is dependent on the cell cycle and zygotic gene activation. Control of HLB growth is achieved by a mechanism integrating nascent mRNAs at the histone locus, which catalyzes phase separation, and the nuclear concentration of Mxc, which is controlled by the activity of cyclin-dependent kinases. Reduced Cdk2 activity results in smaller HLBs and the appearance of nascent, misprocessed histone mRNAs. Our experiments thus identify a mechanism linking nuclear body growth and size with gene expression.