Genome-wide tracking of dCas9-methyltransferase footprints

• DOI: 10.1038/s41467-017-02708-5
• Publication Date: 2018-02-05T13:03:48Z
• Authors: Christina Galonska; Jocelyn Charlton; Alexandra L. Mattei; Julie Donaghey; Kendell Clement; Hongcang Gu; Arman W. Mohammad; Elena K. Stamenova; Davide Cacchiarelli; Sven Klages; Bernd Timmermann; Tobias Cantz; Hans R. Schöler; Andreas Gnirke; Michael J. Ziller; Alexander Meissner
• Keywords: Genome Engineering

In normal mammalian development cytosine methylation is essential and directed to specific regions of the genome. Despite notable advances through mapping its genome-wide distribution, studying direct contribution DNA gene genome regulation has been limited by lack tools for precise manipulation. Thus, combining targeting capability CRISPR-Cas9 system with an epigenetic modifier attracted interest in scientific community. contrast profiling cleavage a nuclease competent Cas9, tracing global activity dead Cas9 (dCas9) methyltransferase fusion protein challenging within highly methylated Here, we report generation use engineered, depleted but maintenance mouse ES cell line find surprisingly ubiquitous nuclear dCas9-methyltransferases. Subsequent experiments human somatic cells refine these observations point important difference between genetic editing that require unique experimental considerations.