GRADUATE SCHOOL OF SCIENCES & ENGINEERING
MOLECULAR BIOLOGY AND GENETICS
PhD THESIS DEFENSE BY BURCU ÖZÇİMEN
Title: The Role of Histone H3 Lysine 36 Methylation in Reprogramming of Fibroblasts and on Induced Pluripotent Stem Cell Generation
Speaker: Burcu Özçimen
Time: August 10, 2018 10.00
Place: SNA A52
Rumeli Feneri Yolu
Thesis Committee Members:
Assoc. Prof. Tamer Önder, Advisor (Koç University, Medical Faculty)
Assoc. Prof. Nathan Lack (Koç University, Medical Faculty)
Assoc. Prof. Tolga Emre (Boğaziçi University, Molecular Biology and Genetics)
Induced pluripotent stem cells (iPSCs) can be obtained from the reprogramming of fully differentiated somatic cells by the introduction of four transcription factors OCT4, SOX2, KLF4 and c-MYC (OSKM). These four transcription factors are sufficient to induce reprogramming but only a few of somatic cells completes this process and attains pluripotency. One important reason for the inefficiency of reprogramming is that despite expressing the ectopically introduced transcription factors, most cells are unable to lose their lineage identity and end up undergoing apoptosis, senescence or cell-cycle arrest. These cell biological processes are thought to be a barrier for reprogramming and their inhibition increases iPSC generation.
Cell type-specific expressions are shown to be under the control of Histone H3 Lysine 36 (H3K36) methylation mark which is present on gene bodies serving as an activating force for transcription elongation. Since those genes are needed to be downregulated at early stage of reprogramming, the H3K36 methylation mark may be a barrier for reprogramming. SETD2 is only known methyltransferase with trimethylating activity of H3K36 residue. Therefore, we examined the influence of SETD2 expression on reprogramming of fibroblasts into iPSCs. Our findings demonstrate that, SETD2 is a barrier for reprogramming and its inhibition enhances iPSC generation by aiding the suppressions of lineage-specific gene expressions in early time points of reprogramming.