Report

Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites

See allHide authors and affiliations

Science  09 Mar 2018:
Vol. 359, Issue 6380, pp. 1166-1170
DOI: 10.1126/science.aan5480
  • Fig. 1 The vast majority of the DNA methylome is maintained 20 min after replication.

    (A) Correlation of methylation frequency between pCs and dCs within the same pdCpGs in pulse. (B) Count of pdCpGs in pulse with differential ΔmC values. (C) Different types of hemiCpGs with all four Cs mapped at least four times. (D) For concordant hemiCpGs in pulse, the distribution of methylation frequency of four Cs in chase is shown (left), and vice versa (right). (E) All concordant hemiCpGs were intersected with WGBS data sets from other human cells. The distribution of ΔmC values is shown for each data set.

  • Fig. 2 HemiCpG is an important component of the DNA methylome.

    (A) Schematic representation of the principles underlying the iSA method. (B) The fraction of all four types of intraCpGs in pulse and chase. (C) The frequency of three types of intraCpGs (with two types of intraCpGshemi combined) at different mouse embryonic stages. ICM, inner cell mass; MEF, mouse embryonic fibroblast; mPGC/fPGC, male/female primordial germ cell. (D) The frequency of three types of intraCpGs at genic regions at different mouse embryonic stages.

  • Fig. 3 Transient interactions between DNMTs and substrate dCs in both maintenance and de novo methylation.

    (A) The fraction of all four types of DNMT-targeted intraCpGs in pulse and chase. (B) Counts of all DNMT-targeted intraCpGshemi-pC in pulse allocated to the appropriate cells according to their methylation frequency in pulse nasBS-seq. (C) Reduction of methylation under DNMT1 KO (24 hours) or DNMT3A/3B double KO (late) is shown for all CpGs, DNMT-targeted intraCpGshemi-pC, and intraCpGsme in pulse and chase and unmapped CpGs. ***P < 0.001. NS, not significant. (D) Distribution of methylation frequency of the four Cs in concordant hemiCpGs viewed through nasBS-seq and DNMT3A/3B nasChIP-BS-seq. The asterisks mark the two Cs inspected in each panel.

  • Fig. 4 Inherited hemiCpGs flanking CTCF/cohesin sites may regulate chromatin interactions.

    (A) Frequency of motif or opposite strand-methylated (same me or oppo me) intraCpGshemi around oriented CTCF motifs co-occupied by CTCF/SMC1A from the two nascent DNA duplexes. Frequency of hairpinCpGhemi from CTCF ChIP-hairpinBS-seq is also shown. (B) All CTCF motifs co-occupied by CTCF/SMC1A in pulse were ranked by their hemi-index. ΔmC of CpGs from the two nascent DNA duplexes and reads per million (RPM) for CTCF and SMC1A nasChIP-seq within a 1-kb window surrounding the motifs are shown. Black in the ΔmC heat maps represents missing data points. (C) All hemiCpGs (ΔmC ≥ 67% or ≤ –67%) from two flanking regions in (B) were retrieved. Methylation frequency of the two Cs in the other dyad in pulse (left) or the same dyad in chase (right) are shown. ***P < 0.001. NS, not significant. (D) The hemi-index of CTCF motifs showing HI > 50 in the pooled data were compared between two dyads, from pulse to chase, and across five passages. (E) Occupancy of WT and R133C mutant MeCP2 in WT mESC, and MeCP2 in DNMT1/3A/3B triple KO (TKO) mESCs was profiled around CTCF motifs showing upstream- or downstream-only hemimethylation in mESCs. (F) The ratio between interaction contacts from Hi-ChIP in WT and DNMT3B-KO HUES64 hESCs emanating from occupied CTCF motifs and extending up to ±1-Mb window is shown.

Supplementary Materials

  • Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites

    Chenhuan Xu and Victor G. Corces

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

    Download Supplement
    • Materials and Methods 
    • Figs. S1 to S10
    • References 

Navigate This Article