NEBNext UltraShear^™ is the only enzymatic fragmentation reagent that we recommend upstream of the EM-Seq workflow. We do not recommend other enzyme-based fragmentation methods as they may affect DNA methylation marks.

For EM-seq^™ use with NEBNext UltraShear^™, please follow the protocol in “Section 3” in the linked manual below.
https://www.neb.com/-/media/nebus/files/manuals/manualm7634.pdf?rev=64e0e81d781748dba43702e4a78da971&hash=09F5E6499849C9045DFAE1A3AB3BDAA9