https://tulab.genetics.ac.cn/author/xiaodi-wu/ Xiaodi Wu Hugo Blox Builder (https://hugoblox.com)en-usMon, 21 Aug 2023 00:00:00 +0000 https://tulab.genetics.ac.cn/media/icon_hu_c372438749b9f15a.png https://tulab.genetics.ac.cn/author/xiaodi-wu/ https://tulab.genetics.ac.cn/publications/2023-natcommun/ Mon, 21 Aug 2023 00:00:00 +0000 https://tulab.genetics.ac.cn/publications/2023-natcommun/ <!-- <div class="alert alert-note"> <div> Click the <em>Cite</em> button above to demo the feature to enable visitors to import publication metadata into their reference management software. </div> </div> <div class="alert alert-note"> <div> Create your slides in Markdown - click the <em>Slides</em> button to check out the example. </div> </div> Add the publication's **full text** or **supplementary notes** here. You can use rich formatting such as including [code, math, and images](https://docs.hugoblox.com/content/writing-markdown-latex/). --> <p>Abstract: The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.</p>