Figure 3. PROSER1 loss leads to aberrant... | American Society of Hematology

Figure 3.

$PROSER1 loss leads to aberrant DNA methylation in hematopoietic progenitors. (A) Quantitation trend plots of DNA methylation quantified by enzymatic methyl sequencing (EM-seq) in gene bodies, non-CGI promoters, and heterochromatin for CpG sites covered by minimum 10 EM-seq reads in all samples in WT, PROSER1 KO, and TET2 KO HOXB8-FL cells. (B) Same as in panel A but showing DNA hypermethylation in CGIs in PROSER1-deficient HOXB8-FL cells. (C) Pie charts showing fraction of hypermethylated (>10% average increase) or hypomethylated (>10% average decrease) CGIs and active enhancers as well as the overlap of active enhancers with altered DNA methylation in PROSER1 KO and TET2 KO HOXB8-FL cells. ∗∗∗∗P < .0001 (2-tailed Fisher exact test). (D) XY scatterplot showing correlation between DNA methylation changes at active enhancers in TET2 (horizontal x-axis) and PROSER1 (vertical y-axis) KO HOXB8-FL cells. Each dot represents average methylation difference of all CpG sites (>10 reads) within a specific enhancer. (E) Box plots showing average enhancer DNA methylation in wild-type, PROSER1 KO, and TET2 KO HOXB8-FL cells at enhancers with >10% hypermethylation in both genotypes (left), PROSER1 KO only (middle), or TET2 KO only (right) cells. Error bars represent the ±min/max, and the line is the median. The effect sizes of DNA methylation change compared to wild-type was measured with Cohen d. ∗d > 0.3 (small effect); ∗∗d > 0.6 (medium effect); ∗∗∗d > 0.9 (large effect). max, maximum; min, minimum; ns, nonsignificant; RR, relative risk; WT, wild-type; UCSC, University of California Santa Cruz.$

PROSER1 loss leads to aberrant DNA methylation in hematopoietic progenitors. (A) Quantitation trend plots of DNA methylation quantified by enzymatic methyl sequencing (EM-seq) in gene bodies, non-CGI promoters, and heterochromatin for CpG sites covered by minimum 10 EM-seq reads in all samples in WT, PROSER1 KO, and TET2 KO HOXB8-FL cells. (B) Same as in panel A but showing DNA hypermethylation in CGIs in PROSER1-deficient HOXB8-FL cells. (C) Pie charts showing fraction of hypermethylated (>10% average increase) or hypomethylated (>10% average decrease) CGIs and active enhancers as well as the overlap of active enhancers with altered DNA methylation in PROSER1 KO and TET2 KO HOXB8-FL cells. ∗∗∗∗P < .0001 (2-tailed Fisher exact test). (D) XY scatterplot showing correlation between DNA methylation changes at active enhancers in TET2 (horizontal x-axis) and PROSER1 (vertical y-axis) KO HOXB8-FL cells. Each dot represents average methylation difference of all CpG sites (>10 reads) within a specific enhancer. (E) Box plots showing average enhancer DNA methylation in wild-type, PROSER1 KO, and TET2 KO HOXB8-FL cells at enhancers with >10% hypermethylation in both genotypes (left), PROSER1 KO only (middle), or TET2 KO only (right) cells. Error bars represent the ±min/max, and the line is the median. The effect sizes of DNA methylation change compared to wild-type was measured with Cohen d. ∗d > 0.3 (small effect); ∗∗d > 0.6 (medium effect); ∗∗∗d > 0.9 (large effect). max, maximum; min, minimum; ns, nonsignificant; RR, relative risk; WT, wild-type; UCSC, University of California Santa Cruz.

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