FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription

Wei Li; Ping Chen; Juan Yu; Liping Dong; Dan Liang; Jianxun Feng; Jie Yan; Peng-Ye Wang; Qing Li; Zhiguo Zhang; Ming Li; Guohong Li

doi:10.1016/j.molcel.2016.08.024

FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription

Mol Cell. 2016 Oct 6;64(1):120-133. doi: 10.1016/j.molcel.2016.08.024. Epub 2016 Sep 22.

Authors

Wei Li¹, Ping Chen², Juan Yu², Liping Dong³, Dan Liang³, Jianxun Feng⁴, Jie Yan⁵, Peng-Ye Wang¹, Qing Li⁴, Zhiguo Zhang⁶, Ming Li⁷, Guohong Li⁸

Affiliations

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 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, 100101; Graduate School of University of Chinese Academy of Sciences, Beijing, China, 100049.
⁴ 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.
⁵ Department of Physics, National University of Singapore, Singapore, 117542; Mechanobiology Institute, National University of Singapore, Singapore, 117411.
⁶ Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
⁷ National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China, 100190. Electronic address: [email protected].
⁸ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, 100101. Electronic address: [email protected].

PMID: 27666592
DOI: 10.1016/j.molcel.2016.08.024

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.

MeSH terms

Amino Acid Sequence
DNA, Fungal / chemistry*
DNA, Fungal / genetics
DNA, Fungal / metabolism
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Gene Expression Regulation, Fungal*
High Mobility Group Proteins / chemistry*
High Mobility Group Proteins / genetics
High Mobility Group Proteins / metabolism
Histones / chemistry*
Histones / genetics
Histones / metabolism
Models, Molecular
Nucleosomes / genetics*
Nucleosomes / metabolism
Nucleosomes / ultrastructure
Protein Folding
Protein Multimerization
Protein Stability
Protein Structure, Secondary
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae / ultrastructure
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Single Molecule Imaging
Transcription, Genetic*
Transcriptional Elongation Factors / chemistry*
Transcriptional Elongation Factors / genetics
Transcriptional Elongation Factors / metabolism

Substances

DNA, Fungal
DNA-Binding Proteins
FACT protein, S cerevisiae
High Mobility Group Proteins
Histones
Nucleosomes
Saccharomyces cerevisiae Proteins
Transcriptional Elongation Factors