Foxp3 and BATF cooperatively direct cis-regulatory programs and gene expression for effector Treg cell...

Area of Science:

• Immunology
• Molecular Biology
• Epigenetics

Background:

• Regulatory T cells (Treg) are crucial for immune suppression.
• The precise mechanisms by which transcription factors (TFs) shape Treg cell heterogeneity are not fully understood.
• Foxp3 is a master regulator of Treg cell function.

Purpose of the Study:

• To elucidate how transcription factors, particularly Foxp3, influence the transcriptional and epigenetic landscapes of Treg cells.
• To investigate the cooperative roles of Foxp3 and BATF in Treg cell differentiation.

Main Methods:

• Simultaneous single-cell chromatin accessibility and transcriptome profiling were employed.
• Topic modeling was used to identify cis-regulatory elements and associated gene expression programs.
• Genome-wide mapping of TF binding sites was performed.

Main Results:

• Foxp3 cooperates with BATF to regulate cis-regulatory programs and gene expression in effector Treg (eTreg) cells.
• Co-binding of Foxp3 and BATF at cis-regulatory elements enhances chromatin accessibility and transcription.
• Foxp3 acts as a context-dependent regulator, interacting with various TFs to orchestrate Treg cell differentiation.

Conclusions:

• Foxp3 and BATF collaboration is essential for eTreg cell differentiation and function.
• Foxp3's regulatory role is context-dependent, involving cooperation or antagonism with other TFs.
• These findings clarify how TF networks shape Treg cell heterogeneity and function.