Generation of the P19 Copg1−/− and Copg2−/− KO cell lines

P19 Copg1^−/− and Copg2^−/− cells were generated by following a CRISPR-Cas9 gene editing strategy. sgRNAs designed to cut in early exons of the Copg1 and Copg2 genes (selected with the CRISPR.MIT tool, see Table S2) were cloned into the pSPCas9(BB)-2TA-GFP vector between the BbsI restriction sites (Ran et al, 2013). P19 cells were transfected with these vectors using Lipofectamine 3000 (Thermo Fisher Scientific) following the manufacturer’s instructions. 72 h after transfection, single GFP-positive cells were sorted and transferred into a 96-well plate using a FACS at the CellNetworks/ZMBH-Flow Cytometry & FACS Core Facility. Clonal cell lines were grown and transferred into larger cell culture dishes and then screened by western blot. Clones that showed absence of γ1-COP or γ2-COP were verified by pCR-Blunt cloning/Sanger sequencing of the target locus.