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English: Several TFs may bind to common gene promoters, or at the same genomic loci. A. In ESCs, different combinations of pluripotency-associated factors, Oct4, Sox2, Nanog, Klf4, Nac1 and Dax1, occupy the promoters of common genes. In this multiple co-occupancy where at least five factors are bound, it typically leads to transcription activation of the target genes, highlighting a synergistic effect that is mediated by a combined positive transcriptional input. B. Multiple TFs are also found to be located on enhancers where these dense ‘hotspots’ are referred as enhanceosomes. As many as 12 factors are found to occupy the enhancer of Oct4, which is a key ESC regulator. Several of these TFs have been shown to biochemically co-purify as part of a larger complex, supporting the synergistic activation model.