Histonchaperones

Histone chaperones are a diverse group of proteins that bind histones and regulate their handling during chromatin assembly and disassembly. They transiently associate with histones, especially H3-H4 dimers and H2A-H2B dimers, to prevent unwanted interactions with DNA and to prevent histone aggregation. Unlike many chromatin enzymes, histone chaperones lack catalytic activity; their primary role is to escort histones to sites of nucleosome assembly, stabilize histone-DNA intermediates, and promote correct nucleosome formation.

Several well-characterized examples exist: CAF-1 (chromatin assembly factor 1) deposits newly synthesized H3-H4 onto replicated DNA in a PCNA-dependent manner. ASF1 (anti-silencing function 1) delivers H3-H4 to various downstream chaperones such as CAF-1 or HIRA. The NAP1 family primarily handles H2A-H2B dimers and buffers histone supply. FACT, a heterodimer of Spt16 and SSRP1, facilitates transcription by temporarily displacing and reassembling H2A-H2B as RNA polymerase passes. HIRA deposits the H3.3 variant independently of DNA replication, guiding variant incorporation at active or poised loci.

Histone chaperones operate during DNA replication, repair, and transcription to ensure chromatin integrity and regulate histone exchange and epigenetic inheritance. They interact with chromatin remodelers and histone-modifying enzymes to coordinate nucleosome assembly with cell-cycle progression and DNA damage response.

Defects or misregulation of histone chaperones can lead to chromatin assembly defects, genomic instability, or altered gene expression, contributing to developmental abnormalities or cancer in some organisms. The family is evolutionarily conserved across eukaryotes, reflecting their fundamental role in chromatin biology.