Crosstalk between DNA methylation Chromatin Structure

ROQUÉ MORENO M; VARGAS ROIG LM

Chromatin Signaling and Diseases

Elsevier

Año: 2016; p. 257 - 268

Regulationof gene expression is the result of a functional crosstalk between multiple epigenetic pathways. DNA methylation is an epigenetic mark that is typically relatedto gene silencing. Changes in DNA methylation are associated with specific histone modifications (other members in the crosstalk), including methylation and acetylation in N-terminal tails. Interestingly, these post-translational histone modifications do not occur at random and are a consequence of the regulated crosstalk with DNA methylation. DNA methylation enzymes direct the histone modification process in a reversible way. Alterations in the crosstalk between DNA and histone modifications can lead to disease, for example, cancer. In the tumorigenic progression, it is proposed that cancer cells may modify their gene expression profile through the accumulation of genetic and epigenetic alterations. These changes affect the pathways that control the cell cycle. At the DNA level, tumors usually present global hypomethylation and tumor suppressor gene hypermethylation. At the histone level, the crosstalk is altered and mis-targeted histone deacetylase activity cause pathological gene silencing. Given the functionally linked crosstalk, the development of drugs that inhibit their interaction would open a promising window for future cancer treatments.