POS0397 AGGREGATED SURVIVIN BINDING AROUND HISTONE H3 EPIGENETIC MODIFICATIONS IN RISK LOCI ASSOCIATED WITH RHEUMATOID ARTHRITIS

Background: Survivin is an integral part of the Chromosomal Passenger Complex (CPC) which plays a vital role in mitosis. Experiments have demonstrated that survivin can physically bind to DNA. Crystallographic studies show binds Threonine-3 histone H3. In patients with autoimmune diseases, increased expression contributes aggravated disease phenotype. Thus, functional, and mechanistic data point potential chromatin regulatory for survivin, possibly combination established gene function carried out by epigenetic modifications (EM). Objectives: The objective study was analyse co-localization bound three H3 – acetylated lysine 27 (K27ac) trimethylated 4 (K4me3) lysine-27 (K27me3). second if survivin-bound DNA sequences overlapped vicinity 106 GWAS SNPs are associated risk developing rheumatoid arthritis (RA). Methods: Chromatin from CD4 T cells 14 female subjects immunoprecipitated antibodies each antibodies, coupled sequencing (ChIPseq, Hiseq2000, Illumina). After mapping annotations sequenced regions human reference genome hg38, enriched peaks were identified through Homer software. ChIP analysed colocalization EMs RA loci, using Bioconductor package ‘ChIPPeakAnno’ RStudio. Results: Among total ~13,000 individual ChIP-peaks, 33% colocalized EM peaks. overlapping linear increase average peak size compared showing no any peak. A maximum 5.5-fold observed when overlap all EMs. major proportion (86%) top either binding or this subset, 63% found within area 100 kilobases preferential enrichment high-scoring colocalizes 3 annotated to, among others, immunological genes CD83, IRF4, CD28, ICOS IL2RA Conclusion: This presents experimental evidence preferentially occurred high density aggregation around its transcription. Since peaks, survivin’s nuclear could immunologically important effects mechanisms diseases. Disclosure Interests: None declared