Quantitative assessment of higher-order chromatin structure of the INK4/ARF locus in human senescent cells

Akiyuki Hirosue, Ko Ishihara, Kazuaki Tokunaga, Takehisa Watanabe, Noriko Saitoh, Masafumi Nakamoto, Tamir Chandra, Masashi Narita, Masanori Shinohara, Mitsuyoshi Nakao

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Somatic cells can be reset to oncogene-induced senescent (OIS) cells or induced pluripotent stem (iPS) cells by expressing specified factors. The INK4/ARF locus encodes p15(INK4b) , ARF, and p16(INK4a) genes in human chromosome 9p21, the products of which are known as common key reprogramming regulators. Compared with growing fibroblasts, the CCCTC-binding factor CTCF is remarkably up-regulated in iPS cells with silencing of the three genes in the locus and is reversely down-regulated in OIS cells with high expression of p15(INK4b) and p16(INK4a) genes. There are at least three CTCF-enriched sites in the INK4/ARF locus, which possess chromatin loop-forming activities. These CTCF-enriched sites and the p16(INK4a) promoter associate to form compact chromatin loops in growing fibroblasts, while CTCF depletion disrupts the loop structure. Interestingly, the loose chromatin structure is found in OIS cells. In addition, the INK4/ARF locus has an intermediate type of chromatin compaction in iPS cells. These results suggest that senescent cells have distinct higher-order chromatin signature in the INK4/ARF locus.

Original languageEnglish
Pages (from-to)553-6
Number of pages4
JournalAging Cell
Volume11
Issue number3
DOIs
Publication statusPublished - Jun 2012

Keywords / Materials (for Non-textual outputs)

  • Cell Aging
  • Cell Line
  • Chromatin
  • Cyclin-Dependent Kinase Inhibitor p16
  • Humans

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