PT  - JOURNAL ARTICLE
AU  - Janssens, Derek H.
AU  - Wu, Steven J.
AU  - Sarthy, Jay F.
AU  - Meers, Michael P.
AU  - Myers, Carrie H.
AU  - Olson, James M.
AU  - Ahmad, Kami
AU  - Henikoff, Steven
TI  - Automated <em>in situ</em> profiling of chromatin modifications resolves cell types and gene regulatory programs
AID  - 10.1101/418681
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 418681
4099  - http://biorxiv.org/content/early/2018/09/16/418681.short
4100  - http://biorxiv.org/content/early/2018/09/16/418681.full
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.