Pioneer transcription factor FoxA maintains an open nucleosome configuration for tissue-specific gene activation [MNase-Seq]. Mus musculus

Nuclear DNA is wrapped around core histones to form nucleosomes, which constrains how transcription factors bind to gene regulatory sequences. Pioneer transcription factors have the special ability to bind target DNA on nucleosomes and initiate gene regulatory events, often leading to a local opening of chromatin. Yet the nucleosomal status of such open chromatin, e.g., at active enhancers, is not clear. Here we develop a combination of low and high levels of MNase digestion along with core histone ChIP-seq to assess the presence of nucleosomes at enhancers and promoters in mouse liver. We find that liver-specific enhancers retain preferentially MNase-accessible nucleosomes, with factors bound, substantially more than ubiquitous enhancers. Furthermore, the pioneer factor FoxA2 is required to keep enhancer nucleosomes accessible in chromatin at active liver genes. Thus, nucleosomes are not exclusively repressive to gene regulation when they are retained with, and exposed by, pioneer factors. Overall design: This experiment includes two technical replicates (F1, F2) of two biological replicates each, examining high and low concentration MNase-seq digestions of adult mouse liver chromatin, either in WT mice or in mice with a deletion of FoxA1 and FoxA2, size-selecting libraries with full nucleosomes or at the sub-nucleosomal size distribution. It does not include sub-nucleosomal sequencing runs for high MNase-seq digestion.