Fig. 6: Schematic model for H3 variant dynamics at chromocenters.

a H3.1/2 and H3.3 variants deposition at chromocenters depends on cell cycle and distinct deposition mechanisms, DNA Synthesis Coupled (DSC) and DNA Synthesis Independent (DSI), respectively. b In a normal ES cell cycle, during G1 phase as the increased transcriptional activity in chromocenter promotes H3.3 deposition by DSI allowing to counteract H3.1/2 enrichment. In S phase, during chromocenter replication, H3.1/2 enrichment is re-established and maintained in G2 prior to cell division. c Forced deposition of H3.3 by DSI throughout cell cycle by targeting HIRA to chromocenter (TALE-HIRA) results in continuous H3.3 deposition and compromises H3.1/2 enrichment at chromocenter. This interference in turn leads to defects in nuclear morphology and cell cycle division.