摘要 : The hierarchical packaging of chromatin fibers plays a critical role in gene regulation.The 30-nm chromatin fibers,a central-level structure bridging nucleosomal arrays to higher-order organizations,function as the first level of ... 展开 The hierarchical packaging of chromatin fibers plays a critical role in gene regulation.The 30-nm chromatin fibers,a central-level structure bridging nucleosomal arrays to higher-order organizations,function as the first level of transcriptional dormant chromatin.The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA.Here,we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome,i.e.,the chromatin fiber reconstituted in the presence of linker histone H5,which shows a two-start left-handed double helical structure twisted by tetranucleosomal units.An atomic structural model of the H5-bound chromatin fiber,including an intact chromatosome,is built,which provides structural details of the full-length linker histone H5,including its N-terminal domain and an HMG-motif-like C-terminal domain.The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber.More importantly,the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions.In addition,we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments.Furthermore,our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber.These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatinfiberwithapolarity invitroand invivo. 收起