Fig. 4

CGGBP1-dependent regulation of cytosine methylation spread by RFM CTCF-binding sites. a to d Cytosine methylation signals in 10 kb flanks of RFM or MFR CTCF-binding sites suggest a barrier-like function for RFM. Upstream and downstream MeDIP-signals at RFM (a) show a weaker correlation (Pearson r² = 0.386) (b) than that at MFR (c), which show higher asymmetry with a better correlation (Pearson r² = 0.738) (d). e to h Cytosine methylation signal asymmetry at HEK293T RFM is lost due to an increase in cytosine methylation downstream (e) or upstream (f) of the CTCF-binding sites. Conversely, the asymmetry is gained due to a decrease in cytosine methylation downstream (g) or upstream (h). i to l The cytosine methylation asymmetry in RFM flanks in GM02639 is stronger than that observed in HEK293T and is lost due to an increase in methylation downstream (i) or (j). Similarly, a much stronger cytosine methylation asymmetry is achieved in GM02639 RFM than the HEK293T RFM due to a decrease in methylation downstream (k) or upstream (l). The stronger asymmetry of MeDIP signal in RFM flanks of GM02639 as compared to HEK293T reinforces lower stochasticity of methylation change caused by CGGBP1 depletion in the former