Structural basis for linker histone H5–nucleosome binding and chromatin fiber compaction

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.

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Publication Details

Journal
Cell Research
Published
2024-08-05
DOI
https://doi.org/10.1038/s41422-024-01009-z
Citations
16
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
3.74

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article

Structural basis for linker histone H5–nucleosome binding and chromatin fiber compaction

Zongjun Mou, Lin Wang, Xue Xiao, Zheng Zhou et al.
16 citations
Cell Research
Genomics and Chromatin Dynamics
3.74
article

Structural basis for linker histone H5–nucleosome binding and chromatin fiber compaction

Zongjun Mou, Lin Wang, Xue Xiao, Zheng Zhou, Juan Yu, Yawen Bai, Huidong Zhang, Mingli Hu, Wei Li, Yan Li, Hui Wang, Min Zhou, Jiacheng Liu, Haonan Zhang, Wenyan Li, Shuming Zhang, Guohong Li, Wei Yu, Linchang Dai, Dongyu Li, Jie Hu, Bing‐Rui Zhou, Feng Song, Ping Zhu, Xin Peng, Jin-Qiu Zhou
article en
16 citations

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.

Cell ResearchVol. 34(10)
National Institutes of Health (US), Sun Yat-sen University (CN), Chinese Academy of Sciences (CN), Sichuan University (CN), Wuhan University (CN), Institute of Biophysics (CN), Center for Excellence in Molecular Cell Science (CN), Institute of Biophysics (BG), National Cancer Institute (US), Institute of Physics (CN), University of Chinese Academy of Sciences (CN), Dezhou University (CN), Eighth Affiliated Hospital of Sun Yat-sen University, Hubei University (CN)
Howard Hughes Medical Institute, National Natural Science Foundation of China, Chinese Academy of Sciences, National Institutes of Health, Department of Science and Technology for Social Development, Fundamental Research Funds for the Central Universities, Institute of Biophysics, Chinese Academy of Sciences, National Cancer Institute
Openalex Percentile: Top 6%
Genomics and Chromatin Dynamics
3.74
DOIOpen Access PDFOpenAlex
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