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Engineered Tn5 Variants Enhance CUT&Tag Fidelity for Transcription Factors

The CUT&Tag method performs exceptionally well for profiling histone modifications, but mapping sequence-specific transcription factors (TFs) is complicated by intrinsic Tn5 activity at accessible DNA, and the high-salt washes used to suppress this activity can destabilize TF-chromatin interactions. We engineered the Tn5 DNA-binding channel to attenuate target-DNA engagement by replacing…

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