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Two familiar colloquial phrases "Dragon Dragon, Phoenix" and "Dragon's Nine Sons Are Different" reveal two key characteristics of biological genetic phenomena: similarity and specificity.
accurate sequencing of the human genome shows that the human genome is very small in differences (-lt;0.3%), which explains the source of genetic similarity; on the other hand, genes are highly organized chromatin structures by a class of biomolecules called histones, which are affected by a variety of factors, including remodeling factors, assembly factors, histones and DNA, as well as histone variants, leading to genetic specificity.
single-molecule manipulation technology is a powerful means to study the dynamic regulation of chromatin.
Institute of Physics of the Chinese Academy of Sciences/Beijing National Center for Condensed Physics Soft Matter Physics Key Laboratory has been gradually establishing a single-molecule research system based on magnetoscopy and fluorescence spectra since 2002, in DNA condensation (JACS 2006, PRL 2012), DNA and anti-cancer drug action (NAR) 2009, PRE 2015), TELOPHIDAL DNA FOLDING (JACS 2013), AND DNA DESMOENZYME MOLECULAR MECHANISMS (EMBOJ 2008, NAR 2015, PRL 2016) HAVE MADE SERIES PROGRESS IN A NUMBER OF TOPICS.
recently, they have made series of progress in cooperation with Li Guohong, National Key Laboratory of Biophysics of the Chinese Academy of Sciences, in cooperation with the National Key Laboratory of Biomoleculars of the Chinese Academy of Sciences, in order to target the problem of the dynamic structure of chromatin fibers. For the first time in the in vitro experimental system,
revealed the dynamic folding process of chromatin fiber, a biomolecular system with complex and advanced structures, and demonstrated the regulatory function of FACT (Comes Chromatin Scription), an important transcription cofactor, at the structural levels of chromatic fibers and nucleosomes. Researchers at the Institute of
Physics have successfully established a single-molecule magnetoscoe measurement platform for high time resolution (2 milliseconds), high spatial resolution (1 nanometer), high-throughput parallel measurement (100 samples) and tracked and analyzed the dynamic process and mechanical basis of chromatin fiber assembly in real time, and found chromatin The fibers form a stable tetrapolymer small body structure unit in the dynamic balance of folding/defolding, and reveals two folding paths of the quad-polymer small body (Figure 1);
the first real-time tracking and analysis of the mechanical basis and dynamics of the dynamic regulation of chromatin fiber structure, and the intermediate structure model of "tetranucleosomes-on-a-string" was proposed on the basis of the original "beads-on-a-string" primary folding model.
this work was published in the 2016 Journal of Molecular Cell (Mol.Cell 64, 120, 2016) and was quoted and reviewed as a cover by Nature Reviews (Nat.Rev. Genet.18, 8, 2017).
Figure 2. FACT's negative regulation of chromatin fibers. The combination of
FACT makes the chromatin fiber very easy to open to the nucleus chain state, easy to transcribe the combination of the machine PolII, for gene transcription preparation.
Figure 3. FACT's dual regulation of nuclear small bodies to reduce stability and maintain its integrity explains fact's ability to coordinate the transcription machine PolII to complete the transcription through the nuclear small body structure, and to help the transcribed nuclear small body restore its structure.
previous work revealed that FACT can help transcription machines overcome the chromatin fiber structure barrier for transcription preparation.
how FACT can help the transcription machine overcome the structural barrier of nuclear small body to successfully complete transcription is the next important issue to be solved.
for this purpose, the researchers used a magnetosesystem to track the effects of FACT combined with nuclear small bodies on the dynamic structure of nuclear small bodies, and clearly revealed that FACT has a unique dual function of reducing the mechanical stability of the structure of the nuclear small body and maintaining the structural integrity of the nuclear small body (Figure 3).
the study analyzed the regulation of the dynamic structure of the nuclear small body in real time, and answered the important question of how the life body completed the transcription efficiently without destroying the integrity of chromatin structure.
just published in the 2018 Journal of Molecular Cell (Mol.Cell 71, 1, 2018).
the series was completed by Li Wei, an associate researcher at the Institute of Physics, and Li Ming, Wang Pengye, as well as researchers Li Guohong and Chen Ping of the Institute of Biophysics.
work has been supported by the National Natural Science Foundation, the Ministry of Science and Technology and the Chinese Academy of Sciences.
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