What Is the Histone Code, and Why Is It Important?

Abstract

Abstract The field of epigenetics is rapidly expanding, and has changed and revised traditional paradigms of inheritance. Epigenetics, literally “beyond genetics” or “in addition to genetics”, is defined as the study of heritable changes in gene expression that occur without a change in DNA sequence. Within this presentation, I will focus on modifications of histones, an important mechanism to convey epigenetic information. Histones, small proteins which serve as spools for DNA wrapped in nucleosomes, are critical regulators of the dynamic state of chromatin. They are subject to numerous posttranslational modifications, including acetylation, methylation, ubiquitylation, and phosphorylation. The best characterized modifications are acetylations and methylations. Increased acetylation of histones by histone acetyltransferases is associated with gene activation due to weakened charge attraction between DNA and histone; histone deacetylases in contrast remove acetyl groups leading to gene inactivation. Histone methylation mediated by histone methyltransferases has either positive effects or negative effects on gene expression depending on location and association of other protein complexes. In general, it is difficult to predict gene regulation based on the study of a single histone modification, since it is the combination of these modifications, also called the histone code, which ultimately controls gene expression. I will discuss details of the histone modification, how they regulate gene expression, and also their relevance in disease, especially breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES4-2.