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There are approximately 250,000 sites in the human cell genome that can be used to initiate DNA replication.
Among them, regarding the relationship between the selection of the DNA replication initiation site and the structure of chromatin, the predecessors in this field inferred a model of DNA replication through some experimental results: it is believed that at the beginning of DNA replication, in the chromatin domain (DNA In the replication domain or topological association domain (TAD), the DNA replication start sites located inside the domain and clustered together have a higher initiation probability (Figure 1 below).
Figure 1: (top) The activity of the DNA replication start site is related to many factors, Michalis et al.
However, this model lacks direct imaging evidence due to technical barriers, including how to accurately label the chromatin domain and its origin of replication based on sequence information at the same time, and compare the domain (radius 200-300 nm) and origin of replication.
Figure 2: The distribution of replication origin sites (purple) in the TAD (green) chromatin topological association structure domain at different periods
At the same time, the researchers found that the spatial distribution of the replication start site in the domain is relatively random when the DNA in the pre-middle stage of G1 has not started to replicate
Combining the above results, the researchers proposed the "Chromatin Re-organization Induced Selective Initiation" (CRISI) model (Figure 3)
Figure 3: The "Chromatin Re-organization Induced Selective Initiation" (CRISI) model establishes the relationship between the selection of the DNA replication initiation site and the changes in the chromatin structure of transcriptional regulation
Researcher Sun Yujie, School of Future Technology, Peking University and Peking University Biomedical Frontier Innovation Center (BIOPIC), is the corresponding author of the research paper
Paper link:
https://genomebiology.
