Chromatin modifier enzymes, the histone code and cancer

Abstract

In all organisms, cell proliferation is orchestrated by coordinated patterns of gene expression. Transcription results from the activity of the RNA polymerase machinery and depends on the ability of transcription activators and repressors to access chromatin at specific promoters. During the last decades, increasing evidence supports aberrant transcription regulation as contributing to the development of human cancers. In fact, transcription regulatory proteins are often identified in oncogenic chromosomal rearrangements and are overexpressed in a variety of malignancies. Most transcription regulators are large proteins, containing multiple structural and functional domains some with enzymatic activity. These activities modify the structure of the chromatin, occluding certain DNA regions and exposing others for interaction with the transcription machinery. Thus, chromatin modifiers represent an additional level of transcription regulation. In this review we focus on several families of transcription activators and repressors that catalyse histone post-translational modifications (acetylation, methylation, phosphorylation, ubiquitination and SUMOylation); and how these enzymatic activities might alter the correct cell proliferation program, leading to cancer.