在后生动物中，调控DNA复制起源的染色质规则仍待进一步研究。我们报告了一项研究结果，即NFIB，核因子I（Nuclear Factor I，NFI）家族的成员，在哺乳动物细胞中与前复制复合物（pre-RC）进行物理结合。基因组分析表明，NFIB通过增加染色质可及性来促进pre-RC的组装。核小体结合和单分子磁镊实验证明NFIB与核小体结合并打开。透射电镜检测表明NFIB促进了母源染色质上的核小体驱逐。NFIB缺陷导致G1期和S期的染色体接触/区块的改变，并影响早期复制领域的某些起源的启动。值得注意的是，与癌症相关的NFIB过表达引发基因复制和基因组变异，模拟了临床乳腺癌中的遗传异常，使癌细胞能够动态演化出生长优势和耐药性。综合这些结果表明，NFIB通过作为基因组组织者的角色有助于促进复制许可，从而为NFIB的生物功能以及真核生物复制起源选择提供了新的线索。© 2023. Springer Nature Limited.

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.© 2023. Springer Nature Limited.