Structure and Function of the Core Histone N-Termini: More Than Meets the Eye

Abstract

For two decades, the core histone N-termini generally have been thought of as unstructured domains whose function is to bind to DNA and screen negative charge. New data indicates that both the molecular mechanisms of action and biological functions of the core histone N-termini in chromatin are considerably more complex. At the level of the chromatin fiber, multiple distinct functions of the N-termini are required to achieve higher order chromatin condensation, two of which apparently involve protein−protein rather than protein−DNA interactions. In addition, the N-termini have been documented to participate in specific interactions with many chromatin-associated regulatory proteins. Here, we discuss evidence supporting the new concepts that when functioning in their natural chromatin context, (1) the N-termini are engaged primarily in protein−protein interactions, (2) as a consequence of these interactions the N-termini adopt specific secondary structure, (3) posttranslational modifications such as acetylation disrupt the ability of the N-termini to form secondary structure, and (4) because the N-termini perform essential roles in both chromatin condensation and also bind specific chromatin-associated proteins, the global structure and function of any given region of the genome will be determined predominantly by the core histone N-termini and their specific interaction partners.