Elucidation of epigenetic action mechanisms of Strip2 involved in differentiation of pluripotent stem cells

There is significant evidence that Strip2 is a key regulator of the differentiation processes of pluripotent embryonic stem cells. However, the epigenetic role of Strip2 in lineage differentiation is quite unknown. In the present study, we investigated the epigenetic mechanisms involved in Strip2-induced differentiation processes using, Chip-seq, promoter assay, Co-IP and global proteomics. Here, we identified protein-protein interactions of Strip2 with the co-repressor proteins of the NuRD/Trim28/HDACs/SETDB1 histone methyltransferase complex which is involved in regulation of the pluripotency of embryonic stem cells. The complex is normally activated by binding of Krueppel-associated box (KRAB) zinc finger proteins (KRAB Zfps) to specific DNA motifs thereby causing methylation of H3 to Lysin-9 residues (H3K9). Notably, our Chip-seq data showed that Strip2 binds to a similar gene motif (20 base pairs) like the KRAB Zfps). We further prove that Strip2 is an epigenetic modifier of the NuRD/Trim28/HDACs/SETDB1 histone methyltransferase complex thereby regulating the differentiation of the pluripotent stem cells.