TET enzymes, TDG and the dynamics of DNA demethylation

“…Indeed, at the center of TET1 ChIP-seq peaks in hESC H1 cells (25), the UM sites occur 26.7 times of expected counts (see details in Materials and Methods), whereas MM motifs occur roughly same (1.4 times) as the expected counts (Figure 2C). This observation is consistent with the previous reports that TETs can be recruited to specific locus by DNA binding factors (60,64). Interestingly, the wide distribution of UM around TET peaks compared to MM-DNMT overlap is consistent with the previously reported role of TET in protecting spanned low-methylation regions termed methylation canyons against hypermethylation (65).…”

“…The methylation level was higher in semen samples than in somatic tissues, indicating a greater fidelity in the maintenance of DNA methylation patterns in the germline, in accordance with previous findings (20,26). Yet, the high similarity of methylomes between semen and drone samples from the same genetic background (i.e., originating from the same individual) suggests a passive, rather than an active (i.e., involving TET enzymes) (38) demethylation in the soma, resulting from loss of methylation by dilution after millions of cell divisions. It is also possible that some changes in DNA methylation patterns can accumulate as a consequence of a drone's ontogeny.…”

“…This observation, which is robust to the cutoffs used to call MTB-DMRs ( Supplementary Fig. 8 ), parallels what has been previously described in differentiating cells and during developmental processes 37–39 despite the fact that the mechanisms controlling active and passive changes in methylation are markedly different 36 . In stark contrast to previous studies that also reported active changes in methylation, for example, in response to neuronal activation 10 or during the process of differentiation of human monocytes into macrophages or dendritic cells 13 , we found a strong association between DMRs and changes in gene expression of nearby genes.…”

“…Indeed, at the center of TET1 ChIP-seq peaks in hESC H1 cells (25), the UM sites occur 26.7 times of expected counts (see details in Materials and Methods), whereas MM motifs occur roughly same (1.4 times) as the expected counts (Figure 2C). This observation is consistent with the previous reports that TETs can be recruited to specific locus by DNA binding factors (60,64). Interestingly, the wide distribution of UM around TET peaks compared to MM-DNMT overlap is consistent with the previously reported role of TET in protecting spanned low-methylation regions termed methylation canyons against hypermethylation (65).…”

“…The methylation level was higher in semen samples than in somatic tissues, indicating a greater fidelity in the maintenance of DNA methylation patterns in the germline, in accordance with previous findings (20,26). Yet, the high similarity of methylomes between semen and drone samples from the same genetic background (i.e., originating from the same individual) suggests a passive, rather than an active (i.e., involving TET enzymes) (38) demethylation in the soma, resulting from loss of methylation by dilution after millions of cell divisions. It is also possible that some changes in DNA methylation patterns can accumulate as a consequence of a drone's ontogeny.…”

“…This observation, which is robust to the cutoffs used to call MTB-DMRs ( Supplementary Fig. 8 ), parallels what has been previously described in differentiating cells and during developmental processes 37–39 despite the fact that the mechanisms controlling active and passive changes in methylation are markedly different 36 . In stark contrast to previous studies that also reported active changes in methylation, for example, in response to neuronal activation 10 or during the process of differentiation of human monocytes into macrophages or dendritic cells 13 , we found a strong association between DMRs and changes in gene expression of nearby genes.…”

“…Indeed, at the center of TET1 ChIP-seq peaks in hESC H1 cells (25), the UM sites occur 26.7 times of expected counts (see details in Materials and Methods), whereas MM motifs occur roughly same (1.4 times) as the expected counts (Figure 2C). This observation is consistent with the previous reports that TETs can be recruited to specific locus by DNA binding factors (60,64). Interestingly, the wide distribution of UM around TET peaks compared to MM-DNMT overlap is consistent with the previously reported role of TET in protecting spanned low-methylation regions termed methylation canyons against hypermethylation (65).…”

“…The methylation level was higher in semen samples than in somatic tissues, indicating a greater fidelity in the maintenance of DNA methylation patterns in the germline, in accordance with previous findings (20,26). Yet, the high similarity of methylomes between semen and drone samples from the same genetic background (i.e., originating from the same individual) suggests a passive, rather than an active (i.e., involving TET enzymes) (38) demethylation in the soma, resulting from loss of methylation by dilution after millions of cell divisions. It is also possible that some changes in DNA methylation patterns can accumulate as a consequence of a drone's ontogeny.…”

“…This observation, which is robust to the cutoffs used to call MTB-DMRs ( Supplementary Fig. 8 ), parallels what has been previously described in differentiating cells and during developmental processes 37–39 despite the fact that the mechanisms controlling active and passive changes in methylation are markedly different 36 . In stark contrast to previous studies that also reported active changes in methylation, for example, in response to neuronal activation 10 or during the process of differentiation of human monocytes into macrophages or dendritic cells 13 , we found a strong association between DMRs and changes in gene expression of nearby genes.…”