Dual function of Polycomb group proteins in T-helper (Th) cells

Aim & Background: The immune system distinguishes between self and non-self but also between different types of non-self, such as bacteria, viruses and worms. Th cells have a fundamental role in that challenge. Following antigen recognition, naive Th cells can differentiate toward one of the several effector lineages, each expressing a distinctive transcriptional profile of cytokines and other lineage specific genes, which eventually instruct the strategy of the immune response. In our lab, we are interested in understanding the mechanisms underlying differentiation and stimulation of these cells. My work is especially focused on exploring in a genome wide manner the binding activity of- and the epigenetic regulation by the polycomb group (PcG) proteins such as the Ezh2 in differentiated Th cells.

Methods: We performed ChIP-Seq and RNA-Seq of in vitro differentiated Th1 and Th2 cells derived from normal and Ezh2-conditionally deficient mice.

Results& Conclusion: We demonstrated that Ezh2 has a dual function as a positive and a negative transcriptional regulator in Th cells; Ezh2 is required for robust expression of the signature transcriptional programs of differentiated Th1 and Th2 cells. We further revealed that Ezh2 possesses a differentiation- and stimulation-dependent binding activity in Th cells, and its binding is correlated with Th1 and Th2 specific transcription factor motifs. We found that Ezh2 is associated also with nascent RNA, and we currently studying the potential