POS0360 COMPLEX LANDSCAPE OF BIRC5/SURVIVIN GENOME BINDING IN HUMAN CD4+ T CELLS

Background: Survivin, coded by BIRC5 gene, is a multitasking protein essential for cell renewal and homeostasis. In autoimmune conditions as rheumatoid psoriasis arthritis, survivin was associated with inflammation severity joint damage. Importantly, inhibition of alleviated experimental arthritis in mice. We have recently shown to be T differentiation micro-RNA processing. The known anti-apoptotic proliferation facilitating functions does not explain the nuclear localization interphase. Objectives: aimed uncover BIRC5/survivin CD4 RA patients healthy. Methods: cells were isolated from peripheral blood using positive selection on magnetic beads (EasySep) activated 48h ConA+LPS. Chromatin immunoprecipitation (ChIP) polyclonal anti-survivin antibodies done four independent samples healthy donors (n=5), smokers (n=3), (n=3) breast cancer (n=2). Pooled libraries constructed each group ChIPseq carried out (Illumina). For comparative RNAseq analysis, incubated or without inhibitor (YM155) 24h. State-of-the-art bioinformatics pipelines applied NGS data survivin-binding peaks used comparison genes, chromatin state annotation functional gene- regulatory regions-based analysis. Co-localization whole genome vicinity differentially expressed genes (DEG) ReMap integrated datasets all human tissues. Results: identified 13 thousands non-overlapping ChIP-peaks (>3000 present at least 3 samples). Survivin-bound regions enriched near promoters (p=e-30 p=e-8), which implied that role transcription could mediated factors. Thus, we analyzed vs binding 1135 regulators (TR) available ReMap. Potential partner proteins selected based enrichment overlapping CD4-active areas. Both, strict overlaps location within 10 100kb peak analyzed. This approach allowed us select >150 TRs tests. involved immunity RA-relevant pathways including cytokine response production, JAK-STAT signaling, etc. Among co-localized CHD8, MAX, EP300, BRD2, CTCF RAD21, responsible architecture. Several massively DEGs after depletion AR, CTCF, MYC IRF1. Search TR motifs supported over-representation sites IRFs (p=e-5) several bZIP-family (p=e-5). Conclusion: Analysis bound DNA demonstrated nonrandom distribution specific elements co-localizeation partners regulate their transcription. Disclosure Interests: None declared