Fig. 1

Schematics illustrating targeted DNA demethylation of H19-DMR to generate SRS model mice. a In mice and humans, Igf2 is normally expressed from the paternal allele, and H19 is expressed from the maternal allele. In patients with SRS, DNA demethylation of H19-DMR results in biallelic expression of H19 and repression of Igf2. b Scheme for CRISPR/Cas9- and SunTag-based induction of demethylation. dCas9 fused to a SunTag (multiple GCN4) can recruit multiple copies of antibody (scFv)-fused TET1CD. Thus, multiple copies of TET1CD hydroxylate specific loci and activate target site-specific demethylation. c Schematic of the mouse H19 locus with four CTCF-binding sites (m1–m4), indicated by green boxes. Locations of gRNA target sites in the H19-DMR are indicated by blue bars. PCR amplified regions and names of primers used for DNA methylation analysis are indicated in red. DNA methylation of CpG sites in CTCF-binding sites (m1–m4) and promotor regions (p1–p4) were analyzed