Chromatin organization and behavior in HRAS-transformed mouse fibroblasts

DOI DOI PDF Web Site 被引用文献2件 参考文献73件

書誌事項

公開日
2024-02-24
資源種別
journal article
権利情報
  • https://www.springernature.com/gp/researchers/text-and-data-mining
  • https://www.springernature.com/gp/researchers/text-and-data-mining
DOI
  • 10.1007/s00412-024-00817-x
  • 10.21203/rs.3.rs-3631068/v1
公開者
Springer Science and Business Media LLC

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説明

<jats:title>Abstract</jats:title> <jats:p>In higher eukaryotic cells, a string of nucleosomes, where long genomic DNA is wrapped around core histones, are rather irregularly folded into a number of condensed chromatin domains, which have been revealed by super-resolution imaging and Hi-C technologies. Inside these domains, nucleosomes fluctuate and locally behave like a liquid. The behavior of chromatin may be highly related to DNA transaction activities such as transcription and repair, which are often upregulated in cancer cells. To investigate chromatin behavior in cancer cells and compare those of cancer and non-cancer cells, we focused on oncogenic-<jats:italic>HRAS</jats:italic> (Gly12Val)-transformed mouse fibroblasts CIRAS-3 cells and their parental 10T1/2 cells. CIRAS-3 cells are tumorigenic and highly metastatic. First, we found that HRAS-induced transformation altered not only chromosome structure, but also nuclear morphology in the cell. Using single-nucleosome imaging/tracking in live cells, we demonstrated that nucleosomes are locally more constrained in CIRAS-3 cells than in 10T1/2 cells. Consistently, heterochromatin marked with H3K9me3 and H3K27me3 was upregulated in CIRAS-3 cells. Finally, Hi-C analysis showed enriched interactions of the B-B compartment in CIRAS-3 cells, which likely represents transcriptionally inactive chromatin. Increased heterochromatin may play an important role in cell migration, as they have been reported to increase during metastasis. Our study also suggests that single-nucleosome imaging provides new insights into how local chromatin is structured in living cells.</jats:p>

収録刊行物

  • Chromosoma

    Chromosoma 133 (2), 135-148, 2024-02-24

    Springer Science and Business Media LLC

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