When the band begins to play: histone acetylation caught in the crossfire of gene control.

Abstract

Increasing evidence from recent research suggests a connection between cancer and a deranged equilibrium of histone acetylation, which is maintained by two competing enzymatic activities, histone acetyltransferases (HATs) and histone deacetylases (HDACs). It is our hypothesis that a significant proportion of leukemias and possibly also solid tumors have abnormalities involving HATs or HDACs at the genomic level through genetic mutations or chromosomal alterations. In these cases, altered levels of HATs or HDACs may derange the tightly regulated equilibrium of histone acetylation, which may affect the expression of a broad spectrum of cellular genes. On the other hand, HATs and HDACs may be carried to defined target promoters as cofactors of transcription factor-bound repressor or enhancer complexes and thereby carry out unwanted enzymatic activities in the wrong place at the wrong time. We therefore propose a model for disease being associated with a deranged equilibrium of acetylation that affects histone proteins and promoter-bound transcription factors.