Mitotic chromosome binding predicts transcription factor properties in interphase.

Area of Science:

• Molecular Biology
• Genetics
• Epigenetics

Background:

• Mammalian transcription factors (TFs) exhibit diverse nuclear mobility and DNA binding affinities.
• Understanding how TF properties influence genomic site occupancy and epigenetic modifications is crucial.
• TF association with mitotic chromosomes is primarily driven by non-specific DNA interactions.

Purpose of the Study:

• To investigate the relationship between TF properties, mitotic chromosome binding (MCB), and genome-wide occupancy.
• To determine how TF mobility and DNA binding kinetics influence their ability to access specific genomic sites.

Main Methods:

• Quantitative measurements of MCB for 501 TFs.
• Fluorescence recovery after photobleaching to assess TF mobility during interphase and mitosis.
• Single-molecule imaging of DNA binding kinetics.
• Mapping of TF binding sites and chromatin accessibility.

Main Results:

• TFs with high MCB are enriched in DNA-rich interphase compartments and show slower mobility.
• MCB strongly correlates with TF on-rates and genome-wide specific site occupancy.
• TF residence times did not correlate with MCB.

Conclusions:

• Non-specific DNA binding properties of TFs are key regulators of their search efficiency.
• These properties dictate the ability of TFs to occupy specific genomic sites and potentially influence epigenetic landscapes.