Rosencrance Celeste D, Walsh Derek
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Nat Commun. 2025 Aug 13;16(1):7507. doi: 10.1038/s41467-025-62921-5.
Human cytomegalovirus extensively alters nuclear organization and the cellular transcriptome, yet understanding of these genome-wide events remains relatively limited. Here, chromatin conformation capture (Hi-C) revealed how cytomegalovirus alters chromosome organization at both large- and small-scales. Nascent transcriptomics further revealed how transcriptional changes correlate with genomic reorganization, while also uncovering infection-induced transcriptional dysregulation that contributes to the induction of neuronal gene signatures in infected fibroblasts. Combining Hi-C and Cleavage Under Targets & Release Using Nuclease (CUT&RUN) we find that viral genomes preferentially localize to highly euchromatic compartments, further dysregulating transcription of host genes. Finally, RNAi-mediated depletion of two key effectors of microtubule-based forces that are exerted on the nucleus provides insights into their diverging roles in regulating compartment-scale contacts and viral genomic interactions with host chromatin. Combined, we reveal the extent to which HCMV interacts with and alters host chromatin and transcription, and the influence of microtubule mechanotransduction on these processes.
人巨细胞病毒广泛改变核组织和细胞转录组，但对这些全基因组事件的了解仍然相对有限。在这里，染色质构象捕获（Hi-C）揭示了巨细胞病毒如何在大尺度和小尺度上改变染色体组织。新生转录组学进一步揭示了转录变化如何与基因组重组相关，同时还发现了感染诱导的转录失调，这种失调导致了感染的成纤维细胞中神经元基因特征的诱导。结合Hi-C和使用核酸酶进行靶向切割与释放（CUT&RUN），我们发现病毒基因组优先定位于高度常染色质区室，进一步失调宿主基因的转录。最后，RNAi介导的对作用于细胞核的基于微管力两个关键效应器的消耗，为它们在调节区室尺度接触以及病毒基因组与宿主染色质相互作用中的不同作用提供了见解。综合起来，我们揭示了HCMV与宿主染色质和转录相互作用并改变它们的程度，以及微管机械转导对这些过程的影响。
