Yin Yang 1-Dependent PcG Function is Essential for TET2 Expression and Early T cell Development.

Area of Science:

• Immunology
• Epigenetics
• Molecular Biology

Background:

• Yin Yang 1 (YY1) is a key transcription factor and Polycomb Group (PcG) protein vital for lymphocyte development.
• The precise epigenetic mechanisms of YY1 in early T-cell development remain unclear.

Purpose of the Study:

• To investigate the role of YY1's PcG function in T-cell development using a conditional knockout mouse model.
• To elucidate the epigenetic pathways regulated by YY1 during T-cell differentiation.

Main Methods:

• CRISPR/Cas9 technology to create a conditional knockout mouse model (Yy1-/ΔREPO).
• Analysis of T-cell development stages, cell proliferation, and apoptosis in knockout mice.
• Assessment of DNA demethylase (TET) gene expression and functional rescue experiments.

Main Results:

• Yy1-/ΔREPO mice exhibited a blockage in T-cell development at the DN3 to SP transition, with DN3 population expansion.
• DN3 cells in knockout mice showed increased proliferation but higher apoptosis rates, reducing SP T cell output.
• YY1 deletion led to downregulation of TET1 and TET2, impacting T-cell differentiation, which was partially rescued by TET2 re-expression.

Conclusions:

• YY1's PcG function is essential for the DN3 to SP T cell transition.
• The YY1-TET2 axis plays a critical role in promoting proper DN3 T-cell differentiation and thymocyte development.