Open chromatin landscape of pancreatic endocrine progenitors

During embryonic development, islet progenitors are specified from pancreatic duct cells by transient expression of Neurog3, a transcription factor necessary and sufficient for initiation of islet development. To understand the dynamics of Neurog3-dependent endocrine cell fate determination, in this study we used ATAC-Seq to identify accessible genomic regions of purified duct, endocrine progenitor, and endocrine cells isolated from mice with varying Neurog3 dosage We bred mice that are wild type, heterozygous or null for Neurog3. In het and null animals, at least one wild type allele of Neurog3 has been replaced with a green fluorescent protein (GFP). Using flow cytometry we purified GFP expressing progenitor cells, endocrine cells, and duct cells from different genotypes and performed ATAC-Seq. We obtained on average 25 million paired-end reads that mapped uniquely to the genome. Our analysis revealed substantial reorganization of accessible regions in progenitor cells when Neurog3 is present. We found "footprints" in the regions that transition from closed to open state during endocrine differentiation and identify targets of Neurog3.