Highlights d Discovery of Spt5-Pol II small-molecule inhibitors (SPIs) that mimic Spt5 knockdown d SPIs relieve promoter-proximal pausing and inhibit inflammatory gene activation d SPIs inhibit mutant huntingtin gene transcription and 3 0 end processing of histone genes d Selective targeting of Spt5-Pol II activities by SPIs uncouples its different functions
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