Elucidation of epigenetic action mechanisms of Strip2 involved in differentiation and tumorigenic potential of pluripotent stem cells
Final Report Abstract
Substantial evidence suggests that Strip2 plays a pivotal role in the differentiation processes of pluripotent embryonic stem cells. However, the epigenetic mechanisms by Strip2 mediate embryonic differentiation and development remain poorly understood. In this study, we identified several interaction partners of Strip2, importantly the co-repressor molecular protein complex nucleosome remodelling deacetylase/Tripartite motif-containing 28/Histone deacetylases/Histone-lysine N-methyltransferase SETDB1 (NuRD/TRIM28/HDACs/SETDB1), which is primarily involved in regulating the pluripotency of embryonic stem cells and its differentiation. The complex is normally activated by binding of Krueppel-associated box zinc-finger proteins (KRAB-ZFPs) to specific DNA motifs, causing H3 to Lysin-9 residues (H3K9) methylation. Our data demonstrate that Strip2 binds to a DNA motif (20 base pairs) similar to KRAB-ZFPs. We establish that Strip2 functions as an epigenetic regulator of pluripotency and differentiation by modulating the activity of KRAB- ZFPs as well as the NuRD/TRIM28/HDACs/SETDB1 histone methyltransferase complex. Using our embryonic stem cell model, we were not able to confirm that Strip2 is involved in the development of cancer diseases. Further experiments are required to prove the relevance of our findings for the differentiation of hiPSCs.
Publications
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Epigenetic mechanisms of Strip2 in differentiation of pluripotent stem cells. Cell Death Discovery, 8(1).
Srinivasan, Sureshkumar Perumal; Nemade, Harshal; Cherianidou, Anna; Peng, Luying; Cruz-Molina, Sara; Rada-Iglesias, Alvaro & Sachinidis, Agapios
