Ultrastable and versatile multimeric ensembles of FoxP3 on microsatellites

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Microsatellites are crucial genomic elements involved in transcriptional regulation.
• FoxP3 is a transcription factor vital for regulatory T cell (Treg) development.
• FoxP3 binds TTTG repeat microsatellites and a wider range of TnG repeats, prompting questions about sequence adaptability.

Purpose of the Study:

• To investigate how FoxP3 adapts to microsatellite sequence variability.
• To explore the role of nucleosomes in FoxP3-DNA interactions.
• To understand the structural plasticity of FoxP3 in coordinating genomic loci.

Main Methods:

• Cryoelectron microscopy
• Single-molecule analyses
• DNA-binding assays

Main Results:

• Murine FoxP3 forms distinct supramolecular structures based on DNA sequence.
• FoxP3 exhibits structural plasticity, enabling it to bridge multiple DNA duplexes (2-4) and form ultrastable complexes.
• Nucleosomes facilitate FoxP3 assembly by bending DNA, promoting the recruitment of distal DNA elements.

Conclusions:

• FoxP3 demonstrates an exceptional ability to adapt its structure to variable microsatellites.
• FoxP3 multimerization can reinforce chromatin boundaries and influence three-dimensional genome architecture.
• The findings reveal a novel mechanism for microsatellite-mediated gene regulation by FoxP3.