Writing and Rewriting the Epigenetic Code of Cancer Cells: From Engineered Proteins to Small Molecules

Abstract

The epigenomic era has revealed a well-connected network of molecular processes that shape the chromatin landscape. These processes comprise abnormal methylomes, transcriptosomes, genome-wide histone post-transcriptional modifications patterns, histone variants, and noncoding RNAs. The mapping of these processes in large scale by chromatin immunoprecipitation sequencing and other methodologies in both cancer and normal cells reveals novel therapeutic opportunities for anticancer intervention. The goal of this minireview is to summarize pharmacological strategies to modify the epigenetic landscape of cancer cells. These approaches include the use of novel small molecule inhibitors of epigenetic processes specifically deregulated in cancer cells and the design of engineered proteins able to stably reprogram the epigenetic code in cancer cells in a way that is similar to normal cells.

Histones: Controlling Tumor Signaling Circuitry

“…In contrast, heterochromatin is condensed and represents areas of the genome that are silenced. Several studies show that alterations in chromatin structure due to histone modifications correlate with gene expression, the cell cycle, DNA replication and damage, DNA repair and chromosome stability [19,20]. …”

“…Epigenetic regulation of gene expression is primarily controlled by histone acetylation and methylation, histone modifications, and changes in nucleosome conformation [20]. There is growing evidence that epigenetics is involved in gene regulation during mammalian development (reviewed in [25]).…”

12 Heredity in the Epigenetic Era: Are We Facing a Politics of Reproductive Obligations?

“…Indeed, altered imprinting is a major new subject in the study of cancer progression and treatment (Blancafort, Jin, and Frye 2013, Suva, Riggi, and Bernstein 2013, Wang and Shang 2013.…”

Methylomes

“…Methylation of the DNA (DNAme) occurs in position 5 in cytosine residues. In mammals, the vast majority (98%) of DNA methylation occurs in CpG (cytosine-phosphate-guanine) dinucleotides in somatic cells [4]. In embryomic stem (ES) cells, however, about one-quarter of all DNA methylation occurs in non-CpG context [4].…”

“…In mammals, the vast majority (98%) of DNA methylation occurs in CpG (cytosine-phosphate-guanine) dinucleotides in somatic cells [4]. In embryomic stem (ES) cells, however, about one-quarter of all DNA methylation occurs in non-CpG context [4]. The haploid human genome contains approximately 29 million CpGs, DNA methylation involves the transfer of a methyl group to cytosine in a CpG dinucleotide through DNA methyltransferases that creates or maintains methylation patterns [3].…”