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Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️ Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬
Using Hcfc1 as a model, we show it functions as a molecular bridge: it connects CGI-bound TFs directly to TFIID. This recruitment overcomes a rate-limiting step unique to CGI promoters, enabling transcription initiation. 🧬🌉