HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia.

ABSTRACT: Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synth

SUBMITTER: Rai TS 

PROVIDER: S-EPMC4265675 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature