RT Journal Article SR Electronic T1 Automated in situ profiling of chromatin modifications resolves cell types and gene regulatory programs JF bioRxiv FD Cold Spring Harbor Laboratory SP 418681 DO 10.1101/418681 A1 Derek H. Janssens A1 Steven J. Wu A1 Jay F. Sarthy A1 Michael P. Meers A1 Carrie H. Myers A1 James M. Olson A1 Kami Ahmad A1 Steven Henikoff YR 2018 UL http://biorxiv.org/content/early/2018/09/16/418681.abstract AB Our understanding of eukaryotic gene regulation is limited by the complexity of protein-DNA interactions that comprise the chromatin landscape and by inefficient methods for characterizing these interactions. We recently introduced CUT&RUN, an antibody-targeted nuclease-cleavage method that profiles DNA-binding proteins, histones and chromatin modifying proteins in situ with exceptional sensitivity and resolution. Here we describe an automated CUT&RUN platform and apply it to characterize the chromatin landscapes of human cell lines. We find that CUT&RUN profiles of histone modifications crisply demarcate active and repressed chromatin regions, and we develop a continuous metric to identify cell-type specific promoter and enhancer activities. We test the ability of automated CUT&RUN to profile frozen tumor samples, and find that our method readily distinguishes two diffuse midline gliomas by their subtype-specific gene expression programs. The easy, cost-effective workflow makes automated CUT&RUN an attractive tool for high-throughput characterization of cell types and patient samples.