Histone Modification in Cancer

Dear Colleagues,

Cancer involves genetic alterations, including mutations, chromosomal abnormalities, genomic instability, and dysregulation of cellular signaling. There are six well-defined events associated with cancer, known as the hallmarks of cancer, which include resisting cell death, sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, and inducing angiogenesis. Recent research suggests that epigenetic regulation is possibly involved in the formation of cancer progenitor cells. In addition, epigenetic mechanisms may regulate many aspects of these six hallmarks of cancer. Epigenetic drugs are expected to reduce cancer relapse as a component of combination therapy, as they have the potential to kill cancer progenitor cells and drug resistant cancer cells. Epigenetic mechanisms are usually reversible and include histone modification and DNA methylation. Acetylation and deacetylation of histones provide an open or closed chromatin conformation, which facilitate or inhibit transcription, respectively. In contrast, methylation of the lysine and arginine residues of histones could be activating or inhibitory depending on where the methylation occurs. There are specific histone methylases which perform this function. In addition to methylation, several other modifications in histones regulate gene expression. Other modifications include phosphorylation, ubiquitination, and sumoylation. Histone modifications are also known to recruit DNA methylation enzymes at the site of methylation. Additionally, histone modifications are involved in creating an insulation zone around enhancer-promoter regions by recruiting CTCF, which plays an important role in tissue specific gene expression. Histone modifications also seem to play a significant role in development. Aberration of this process could be involved in carcinogenesis. The current Topical Collection entitled, “Histone Modifications,” is designed to include articles that will address these issues.

Dr. Sibaji Sarkar
Collection Editor

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