alexa Chemical regulation of epigenetic modifications: opportunities for new cancer therapy.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Genetic Syndromes & Gene Therapy

Author(s): Zheng YG, Wu J, Chen Z, Goodman M

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Abstract Epigenetics is concerned about heritable changes in gene expression without alteration of the coding sequence. Epigenetic modification of chromatin includes methylation of genomic DNA as well as post-translational modification of chromatin-associated proteins, in particular, histones. The spectrum of histone and non-histone modifications ranges from the addition of relatively small groups such as methyl, acetyl and phosphoryl groups to the attachment of larger moieties such as poly(ADP-ribose) and small proteins ubiquitin or small ubiquitin-like modifier (SUMO). The combinatorial nature of DNA methylation and histone modifications constitutes a significant pathway of epigenetic regulation and considerably extends the information potential of the genetic code. Chromatin modification has emerged as a new fundamental mechanism for gene transcriptional activity control associated with many cellular processes like proliferation, growth, and differentiation. Also it is increasingly recognized that epigenetic modifications constitute important regulatory mechanisms for the pathogenesis of malignant transformations. We review here the recent progress in the development of chemical inhibitors/activators that target different chromatin modifying enzymes. Such potent natural or synthetic modulators can be utilized to establish the quantitative contributions of epigenetic modifications in DNA regulated pathways including transcription, replication, recombination and repair, as well as provide leads for developing new cancer therapeutics. This article was published in Med Res Rev and referenced in Journal of Genetic Syndromes & Gene Therapy

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