Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic...

Area of Science:

• Immunology
• Developmental Biology
• Molecular Genetics

Background:

• Runt domain-related (Runx) transcription factors are crucial for T cell development.
• Runx1 has been considered the dominant factor, but its precise role alongside Runx3 is less understood.

Purpose of the Study:

• To investigate the collaborative and redundant functions of Runx1 and Runx3 in T cell development.
• To elucidate how Runx factors regulate gene expression dynamically during T cell lineage commitment.

Main Methods:

• Utilized Cas9 gene editing for single and double Runx knockouts in mice.
• Analyzed gene expression and transcription factor binding site occupancy during T cell development stages.

Main Results:

• Runx1 and Runx3 are coexpressed, share overlapping genomic binding sites, and exhibit redundant functions.
• These factors dynamically activate T-lineage genes and repress progenitor genes during commitment.
• Runx binding sites and partner factor cobinding patterns shift stage-dependently, contributing to irreversible commitment.

Conclusions:

• Runx1 and Runx3 act collaboratively and redundantly, with stage-specific functions, to drive T cell development.
• Dynamic regulation of gene expression and binding site occupancy by Runx factors ensures irreversible lineage commitment.