Journal
JOURNAL OF CELL SCIENCE
Volume 118, Issue 6, Pages 1321-1330Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.01709
Keywords
nuclear structure; three-dimensional culture; breast; morphogenesis; quiescence; heterochromatin protein 1
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Funding
- NCI NIH HHS [CA64786, R01 CA064786, R01 CA064786-05, R37 CA064786] Funding Source: Medline
- NIA NIH HHS [AG09909, T32 AG000266, R37 AG009909, R56 AG009909, AG00266, R37 AG009909-10] Funding Source: Medline
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Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those occurring during differentiation and growth arrest. Using human mammary epithelial cells in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNase, but not RNase, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein 1 gamma. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in human mammary epithelial cells. Here we show that a novel extra-telomeric organization of TIN2 is associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.
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