Written by |Zhu Bing(Institute of Biophysics, Chinese Academy of Sciences) The basic unit of chromatin in eukaryotes is the nucleosome. The DNA is wound around a histone octamer consisting of one histone (H3-H4)2 tetramer and two H2A-H2B dimers 1 3 4 turns to form a nucleosome structure. DNA replication obviously requires the DNA to be stripped from the histone octamer, but the replication fork requires the newly isolated DNA and histones to reunite and re-form the nucleosome structure. The completion of this process has always been an important scientific problem in the field of molecular biology, because nucleosomes are carriers of epigenetic information, and the re-evaluation of old nucleosomes is of great significance for the inheritance accuracy of epigenetic information. This question can be broken down into a number of specific questions:1How are old nucleosomes assigned to two sister chromatids after replication? Can they go back to where they were in the DNA? 2.How are histones in old nucleosomes distributed after replication? Will they regroup or will they stay together? What are the basic units of their repurposing? 3.What are the molecular mechanisms that ensure the reuse of old nucleosomes during replication-coupled nucleosome assembly? On the first question, the consensus in the field is:Old nucleosomes are distributed almost equally between the two sister chromatids, not far from their original positions, but the mechanism is still not fully understood. Regarding the second question, our group found more than 10 years ago that the histone (H3-H4)2 tetramer in the old nucleosome basically does not dissociate during replication, but H2A-H2B does. So the basic unit of old nucleosome reuse will not be a histone octamer, but will it be a (H3-H4)2 tetramer or a histone hexamer composed of a (H3-H4)2 tetramer and an H2A-H2b dimer? With regard to the third question, it is known that MCM2 in the MCM complex can help reuse histones H3 and H4 in old nucleosomes, and that the FACT complex is also involved in replication-coupled nucleosome assembly, but the specific mechanism is unknown. Two studies, published on March 7, 2024, answer the unresolved parts of these questions. science china life scienceThe letter column of the journal was published in the Institute of Biophysics, Chinese Academy of SciencesXu RuimingThe research group is entitled ".structure of a histone hexamer bound by the chaperone domains of spt16 and mcm2The article published the crystal structure of the complex of the human FACT complex subunits SPT16, MCM2 and histones. The structure indicatesThe repurposed unit of the old nucleosome should be made up of one (h3-h4).A histone hexamer consisting of a tetramer and an H2A-H2B dimer. This is somewhat surprising because once the DNA is stripped from the histone octamer, the H2A-H2B dimer will be detached from the (H3-H4)2 tetramer at normal salt concentrations. Interestingly, the SPT16 protein in the FACT complex binds to both the (H3-H4)2 tetramer and an H2A-H2B dimer, while the MCM2 binds to the (H3-H4)2 tetramer at the position previously occupied by the dislodged H2A-H2b dimer, which together stabilizes the histone hexamer structure. Last year,Xu RuimingwithLi GuohongZhu Bingand other research groupsscienceThe journal published the structure of the CAF1 complex responsible for assembling new nucleosomes during replication (see Bioart report for details: Expert CommentsScience丨Xu Ruiming, Li Guohong, Zhu Bing, Liu Chaopei reveal the structural basis of the chromatin assembly factor CAF-1 mediating nucleosome assembly). These two works complement each other and reveal the mechanism of nucleosome assembly between old and new nucleosomes that are replicated and conjugated. 
Dr. Gan Songlin and Assistant Researcher Yang Wensi from the Institute of Biophysics, Chinese Academy of Sciences co-authored the article, and Researcher Xu Ruiming is the corresponding author. On the same day,natureThe University of Hong Kong was published in the journalZhai Yuanliang, Peking UniversityGao NingLi Qingand Cornell UniversityDai Bi XuanThe research group jointly published a paper entitled ".parental histone transfer caught at the replication fork(see BioArt's tweet of the day for details), published the replicatosome structure of yeast, in which the complex structure of SPT16, MCM2 and histone hexamer partially coincides with that of the Xu Ruiming group, indicating that this mechanism is conserved from yeast to human. In addition to the mutual corroboration of the work of Xu Ruiming's group, the analysis of the clone structure also answers another question I mentioned earlier, why the old nucleosomes can return to their original positions after replication. Because the molecular machinery responsible for the depolymerization and reuse of old nucleosomes is part of the replicat, the histones of the old nucleosomes naturally remain in the replicator and are further presented to a place close to the original position on the DNA substrand that has just been replicated. 
Li Ningning, School of Life Sciences, Peking University, is the first author of the article, and Zhai Yuanliang, Assistant Professor of the School of Biological Sciences of the University of Hong Kong, Professor Gao Ning and Professor Li Qing of the School of Life Sciences, Peking University, and Professor Dai Bijun of Cornell University are the co-corresponding authors. Original link:
Hotspot Engine Program