Downregulation of UCHL1 by epigenetic editing suppresses the expression of COL1A1 and fibronectin. (a, b). DNA methyltransferase tools to downregulate UCHL1. HEK293T (a) and H1299 (b) cells were cotransfected with 1 µg UCHL1 sgRNA (#1/2/3) and 2 µg (in total) dCas9-mcherry-ED(s). For mCherry-based enrichment, cells were collected 60 h after transfection and dCas9-mCherry-ED expressing cells were sorted by FACS. Half of the sorted cells were harvested for short-term (day 2) expression measurements and the remaining cells were seeded in 24-well plates for long-term expression (day 12 for HEK293T, day 16 for H1299). (c, d). same as (A, B), genomic DNA at day 2 (left panel) and day 12/16 (right panel) was isolated from HEK293T (A) or H1299 (B) sorted cells, simultaneously with total RNA isolation, and used for pyrosequencing. dCas9-MSssI (E186A)-mCherry (inactive mutant); dCas9-MSssI (Q147L)-mCherry (active mutant). (e, f). H1299 cells were co-transfected with 1 µg a mixture of UCHL1 sgRNA (#1/2/3) and 2 µg dCas9-EZH2-mCherry or dCas9-NED-mCherry by PEI. Cells were collected 48 h post transfection, and mCherry-positive cells were sorted by FACS. The mRNA expression of UCHL1 (e), COL1A1, and fibronectin (f) were analysed by real-time qRT-PCR (n = 3). Significance was analysed by one-way ANOVA, *p < 0.05, **p < 0.