Figure 3.

Disruption of mdig gene elevates the level of H3K9me3 on the imprinted H19-IGF2 loci and the genes involved in lung fibrosis. A. ChIP-seq shows an increased enrichment of H3K9me3 in the imprinting control region and promoter regions of the H19-IGF2 loci in the mdig KO cells. Bottom panel shows that this enrichment of H3K9me3 is correlated with a reduced expression of H19 as evidenced by RNA-seq. B. Mdig KO cells exhibited enhanced H3K9me3, H3K27me3, and/or reduced H3K4me3 on the collagen genes involved in lung fibrosis. This histone methylation profile is associated with an overall reduced expression of collagen genes in the KO cells as determined by RNA-seq. C & D. Mdig knockout increased H3K9me3 (C) and decreased expression (RNA-seq, D) of the key genes in TGFβ signaling.