EndoC-βH1 multiomic profiling defines gene regulatory programs intrinsic to human β cell identity and function. Homo sapiens isolate:Human pancreatic islets, EndoC-ßH1 cells

EndoC-βH1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of normal islet function as well as beta cell failure in diabetes. However, comprehensive knowledge of its (epi)genomic landscape has been lacking. Here, we report extensive chromosomal (spectral karyotyping), genetic (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), and transcriptomic (RNA-seq, miRNA-seq) maps of this cell model. Integrated analyses of these maps define beta cell-specific chromosome territories and transcriptional cis-regulatory programs and identify allelic effects on cis-regulatory element use and expression. Importantly, comparative analyses with maps generated in human islets/beta cells indicate substantial preservation of cis-regulatory element use and chromatin looping. Together, these maps and an interactive web application we have created for their exploration are important tools for the design and completion of experiments to probe and manipulate the genetic programs governing beta cell identity and (dys)function in diabetes.