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DynaTag Maps Transcription Factor–DNA Interactions at Single-Cell Resolution and Uncovers Chemotherapy Resistance Dynamics

The physiological salt-buffer protocol preserves fragile transcription factor contacts during nuclei handling to reveal shifting occupancy patterns undetectable by conventional high-salt methods.

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Overview

  • DynaTag outperforms existing methods such as ChIP-seq and CUT&RUN by delivering superior sensitivity and resolution in low-input and single-cell samples.
  • It employs a physiological intracellular salt solution throughout all nuclei handling steps to retain specific transcription factor–DNA interactions while suppressing nonspecific binding.
  • Researchers applied DynaTag to profile 15 transcription factors in mouse embryonic stem cells, revealing dynamic binding shifts of NANOG, MYC and OCT4 during cell-state transitions.
  • In a patient-derived mouse model of small cell lung cancer, chemotherapy-resistant tumors showed elevated FOXA1 and MYC occupancy alongside declines in ASCL1 and POU2F3 binding.
  • The method’s ability to generate high-resolution maps from scarce or clinical samples opens new avenues for studying epigenetic regulation across development, disease and treatment response.