Fig. 15
From: Epigenetic tumor heterogeneity in the era of single-cell profiling with nanopore sequencing
The linkage between DNA methylation and histone modification in pluripotency genes. In embryonic stem cells, pluripotency genes such as Oct 3/4 and Nanog have acetylated (unmethylated) CpG islands. These islands are combined with acetylated Histones (Ac) H3 and H4 and methylated (Me) lysine 4(K4) of Histone H3. With the initiation of differentiation histone methyltransferase (G9a) together with histone deacetylase (HDAc) enzyme binds to the complex. The binding leads to deacetylation of H3 and H4. At the same time demethylation of K4 is catalyzed by HDAc and methylation of K9 is catalyzed by G9a. This modification created a binding site for the chromodomain protein heterochromatin protein 1(HP1). Finally, G9a recruits the methylases DNMT3A and DNMT3B (dark purple circles), which will mediate the de novo methylation of the deacetylated DNA [232, 234]. The process favors epigenetic silencing and methylation while blocking heterochromatinization. Image reprinted from [235] with permission of the publisher (Request ID 600061575 25 Nov 2021)