FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription
Wei Li1,8, Ping Chen2,8, Juan Yu2, Liping Dong2,3, Dan Liang2,3, Jianxun Feng6, Jie Yan4,5, Peng-Ye Wang1, Qing Li6, Zhiguo Zhang7, Ming Li1, Guohong Li2,9

1 National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China, 100190.
2 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, 100101.
3 Graduate School of University of Chinese Academy of Sciences, Beijing, China, 100049.
4 Department of Physics, National University of Singapore, Singapore, 117542.
5 Mechanobiology Institute, National University of Singapore, Singapore, 117411.
6 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China 100871.
7 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.

Abstract

        In eukaryotes, the packaging of genomic DNA into chromatin plays a critical role in gene regulation. However, the dynamic organization of chromatin fibers and its regulatory mechanisms remain poorly understood. Using single-molecule force spectroscopy, we reveal that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. The stability of the tetranucleosomal unit is attenuated by histone chaperone FACT (facilitates chromatin transcription) in vitro. Consistent with in vitro observations, our genome-wide analysis further shows that FACT facilitates gene transcription by destabilizing the tetranucleosomal unit of chromatin fibers in yeast. Additionally, we found that the linker histone H1 not only enhances the stability but also facilitates the folding and unfolding kinetics of the outer nucleosomal wrap. Our study demonstrates that the tetranucleosome is a regulatory structural unit of chromatin fibers beyond the nucleosome and provides crucial mechanistic insights into the structure and dynamics of chromatin fibers during gene transcription.

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