Induced deposition of the histone variant H3.3 in interferon stimulated genes

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NICHD	EPIGEN/TRANS/CHROM-12

Authors

• N Sarai
• K Nimura
• T Tamura
• T Kanno
• M Patel
• N Ayithan
• K Ura
• K Ozato

Abstract

Core histones are synthesized and deposited onto the genome during S phase. In contrast, the histone variant, H3.3 is synthesized and deposited in non-S phase. Since deposition of H3.3 occurs in the transcriptionally active chromatin regions, H3.3 is thought to play an important role in epigenetic control of some genes. However, mechanism of H3.3 enrichment during active transcription is still unclear. Using a YFP-tagged H3.3 expression vector, we studied H3.3 deposition in type I interferon (IFN) stimulated genes (ISGs) in fibroblasts after IFN beta stimulation. We found that the deposition of H3.3 is mainly observed in the distal end of coding region, and H3.3 is stably remained for days after IFN beta stimulation. We also found that the deposition pattern of H3.3 correlates with H3K36 trimethylation. Furthermore, a mutant H3.3 not methylated at K36 was not deposited in ISGs. We knocked down H3.3 mRNA expression by shRNA, and found that ISG mRNA induction was reduced in H3.3 knockdown cells. In conclusion, IFN stimulation triggers prolonged H3.3 deposition in ISGs. H3.3 deposition was linked to and likely depends on trimetylation of the K36. Finally, H3.3 deposition is integral to ISG transcription and plays a critical role in regulating IFN’s biological activities.

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