Transcription factor FoxA (HNF3) on a nucleosome at an enhancer complex inliver chromatin

Nucleosome-like particles and acetylated histones occur near active promote rs and enhancers, and certain transcription factors can recognize their tar get sites on the surface of a nucleosome in vitro; yet it has been unclear whether transcription factors can occupy target sites on nucleosomes in nat ive chromatin. We developed a method for sequential chromatin immunoprecipi tation of distinct nuclear proteins that are simultaneously cross-linked to nucleosome-sized genomic DNA segments. We find that core histone H2A co-oc cupies, along with the FoxA (hepatocyte nuclear factor-3) transcription fac tor, DNA for the albumin transcriptional enhancer in native liver chromatin , where the enhancer is active. Because histone H2A on nuclear DNA is only known to exist in nucleosomes, we conclude that transcription factors can f orm a stable complex on nucleosomes at an active enhancer element in. vivo.