Two surfaces on the histone chaperone Rtt106 mediate histone binding, replication, and silencing

摘要

In each human cell, ~2 m of DNA is packaged into a nucleus a few microns in diameter. To accomplish this task, 146 bp of DNA is wrapped around a complex of eight histone proteins to form a compact structure called a nucleosome. Nucleosomes and other associated proteins, referred to collectively as chro-matin, then fold into higher order structures whose precise architecture is not well described. Chromatin organization is regulated by chemical modifications to histones, such as adding an acetyl or methyl group to the lysine (a positively charged amino acid) at certain positions, which modulate interactions between neighboring histones, between histones and DNA, and between histones and chromatin-associated proteins. Because of their extensive positive (basic) charge, when histones are not bound to DNA, they are prone to promiscuous nonspecific interactions that can reduce cellular fitness. Histone chaperones are proteins that bind histones to prevent these adverse effects and play an important role in regulating all DNA-dependent processes. We studied the histone chaperone Rtt106, which regulates the assembly of modified histones into chroma-tin as DNA is replicated and transcribed. Using X-ray crystallography, yeast genetics, and biochemistry, our study defined how Rtt106 interacts with histones, the specificity of these interactions in cells, and their functional consequences.