JAK2V617F leads to 5-hmC gain in vivo that correlates with gene expression. JAK2V617F leads to 5-hmC gain in vivo that correlates with gene expression.

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JAK2V617F leads to 5-hmC gain in vivo that correlates with gene expression. JAK2V617F leads to 5-hmC gain in vivo that correlates with gene expression. A and B, Mice with transgenic expression of constitutively active form of JAK2 (Jak2V617F) and wild-type (WT) controls were used to isolate erythroid progenitor cells (sorted CD71+) from marrow and spleen. RNA-seq was performed and bioinformatics analysis revealed greater numbers of differential expression of transcripts as well as overexpressed transcripts in Jak2V617F samples compared with the WT mice. C, 5-hMe-Seal assay was performed for whole-genome 5-hmC analysis, which revealed increased accumulation of 5-hmC peaks in Jak2V617F mice erythroid samples. Differential 5-hmC gain was calculated in 2 Jak2V617F and 2 WT mice. D, A colocalization plot combining 5-hmC and gene expression was constructed showing the coverage of the RNA-seq samples within the regions defined by the 5-hmC peaks. Positive colocalization of expressed transcripts was seen around 5-hmC peaks and this was more pronounced in Jak2V617F samples. E and F, Plotsshowing increased expression of Gata1 and Cxcr2 in Jak2V617F samples with increased gain of 5-hmC at their promoters in Jak2V617F samples is seen.G, Differential 5-hmC regions in Jak2V617F samples were correlated with differentially expressed genes in human JAK2V617F samples. A positive correlation was seen between murine and human samples on GSEA. Jong Jin Jeong et al. Cancer Discov 2019;9:778-795 ©2019 by American Association for Cancer Research