Epigenetic effects of survivin and histone modifications in human CD4+ T cells

Abstract

The purpose of this thesis is to elucidate the effects of survivin deprivation on CD4+ T cells through the analysis of histone modifications. In particular, the intent is to investigate whether or not survivin affects acetylation of lysine 27 in histone H3, tri-methylation of lysine 4 in histone H3 or tri-methylation of lysine 27 in histone H3 on a genome-wide scale, as well as explore what impact any such effects may have on cellular processes. To this end, direct investigation, two interpretive strategies and gene ontology analysis were employed in the analysis of chromatin immunoprecipitation sequencing data obtained from survivin deficient and sufficient CD4+ T cells. It was discovered that depletion of survivin increases the number of H3K27me3 marks and potentially transitions the CD4+ T cells into a more transcriptionally repressed state. Lesser increases in H3K27Ac marks were also uncovered, as well as an association between the shifts in histone marks and cell-cell adhesion processes. It can be concluded that survivin deprivation does affect the histone modification profile of CD4+ T cells and that these changes are associated with cell-cell adhesion on a biological process level.