Download MendeleyStructural basis for linker histone H5-nucleosome binding and chromatin fiber compaction.
Li, W., Hu, J., Song, F., Yu, J., Peng, X., Zhang, S., Wang, L., Hu, M., Liu, J.C., Wei, Y., Xiao, X., Li, Y., Li, D., Wang, H., Zhou, B.R., Dai, L., Mou, Z., Zhou, M., Zhang, H., Zhou, Z., Zhang, H., Bai, Y., Zhou, J.Q., Li, W., Li, G., Zhu, P.(2024) Cell Res
- PubMed: 39103524
- DOI: https://doi.org/10.1038/s41422-024-01009-z
- Primary Citation of Related Structures:
8XJV - PubMed Abstract:
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 chromatin fiber with a polarity in vitro and in vivo.
Organizational Affiliation:
Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
