Open AccessQuantitative assessment of higher‐order chromatin structure of the INK4/ARF locus in human senescent cells
Author(s) -
Hirosue Akiyuki,
Ishihara Ko,
Tokunaga Kazuaki,
Watanabe Takehisa,
Saitoh Noriko,
Nakamoto Masafumi,
Chandra Tamir,
Narita Masashi,
Shinohara Masanori,
Nakao Mitsuyoshi
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2012.00809.x
Subject(s) - ctcf , biology , chromatin , locus (genetics) , bivalent chromatin , reprogramming , microbiology and biotechnology , genetics , gene , enhancer , gene expression , chromatin remodeling
Summary 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.