1. The bottom panel depicts the "breakdown" of the barriers in a cancer cell such that the transcriptionally repressive chromatin and DNA methylation all have spread into the CpG island promoter region and correlate with transcriptional repression (red arrow with x) of the gene. The DNA methylating complex now has access to the region, and the transcriptional machinery (CoA, HAT, and TF) is excluded. The switch from an actively transcribed, unmethylated promoter region to inactive, heavily methylated regions may occur through alternative intermediates. On the left, one possible transition occurs with initial increases in DNA methylation (with accompanying MBPs) prior to changes in the histone code or nucleosome positioning. MBPs would then recruit repressive complexes, including HDACs, which would lead to histone modification. Alternatively, the right side of the figure shows the initial alteration in histone and nucleosome structure, which precedes changes in DNA methylation. In this progression, the repressive complexes could recruit DNMTs, which would subsequently lead to increases in DNA methylation.
Source: DNA Methylation and Epigenetic Silencing of Genes in Cancer, The Online Metabolic and Molecular Bases of Inherited Disease
Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: Accessed: October 17, 2017
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