Abstract
Chromatin is the complex of eukaryotic DNA and proteins required for the efficient compaction of the nearly 2-meter-long human genome into a roughly 10-micron-diameter cell nucleus. The fundamental repeating unit of chromatin is the nucleosome: 147bp of DNA wrapped about an octamer of histone proteins. Nucleosomes are stable enough to organize the genome yet must be dynamically displaced and reassembled to allow access to the underlying DNA for transcription, replication, and DNA damage repair. Histone chaperones are a non-catalytic group of proteins that are central to the processes of nucleosome assembly and disassembly and thus the fluidity of the ever-changing chromatin landscape. Histone chaperones are responsible for binding the highly basic histone proteins, shielding them from non-specific interactions, facilitating their deposition onto DNA, and aiding in their eviction from DNA. Although most histone chaperones perform these common functions, recent structural studies of many different histone chaperones reveal that there are few commonalities in their folds. Importantly, sequence-based predictions show that histone chaperones are highly enriched in intrinsically disordered regions (IDRs) and acidic stretches. In this review, we focus on the molecular mechanisms underpinning histone binding, selectivity, and regulation of these highly dynamic protein regions. We highlight new evidence suggesting that IDRs are often critical for histone chaperone function and play key roles in chromatin assembly and disassembly pathways.