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Researchers at IBP Revealed That FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription by Single Molecule Spectroscopy

Author: Update time: 2016-09-28

Eukaryotic DNA is hierarchically packaged into chromatin, in which the dynamics of chromatin fibers play a central role in DNA-related biological processes, such as transcription, DNA replication, recombination, and repair. However, the dynamic organization of chromatin fibers and its regulatory mechanisms remain poorly understood. The highly dynamic and heterogeneous properties of chromatin fibers impose various technical challenges to probe the detailed structure and dynamics of chromatin fibers using traditional biochemical assays.  

The research group led by Prof. LI Guohong at the Institute of Biophysics, Chinese Academy of Sciences, mainly focuses on the investigation of epigenetic regulations of chromatin higher-order structures and their biological functions in gene regulation and cell fate determination. They have successfully developed an in-vitro chromatin reconstitution and structural analysis platform, and previously determined the 3D cryo-EM structures of 30-nm chromatin fibers containing linker histone H1, which revealed a left-handed double helical structure twisted with tetranucleosomal units (Song et al., Science, 2014).  

In this study, by collaborating with Prof Ming Li’s group in the Institute of Physics, the research team revealed that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. By using single-molecule force spectroscopy, they demonstrated that mechanical unfolding of a 30-nm fiber is a multi-step process and the tetranucleosomeson- a-string is a distinct intermediate of chromatin. In addition, the stability of the tetranucleosomal unit is attenuated by histone chaperone FACT (facilitates chromatin transcription) in vitro, which is consistent with the genome-wide analysis showing that FACT facilitates gene transcription by destabilizing the tetranucleosomal unit of chromatin fibers in yeast. Their results demonstrated 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. 

This study, entitled “FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription”, was published online in Molecular Cell on September 22, 2016. The work was supported by the Ministry of Science and Technology of China, the National Natural Science Foundation of China and the Chinese Academy of Sciences. 

Figure: Tetranucleosome is a stable secondary structural unit of chromatin fibers and negatively regulated by FACT for transcription (Image by IBP) 

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LI Guohong 

National Laboratory of Biomacromolecules 

Institute of Biophysics 



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