Higher order nuclear organization in growth arrest of humanmammary epithelial cells: A novel role for telomere-associated proteinTIN2
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 which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) 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 l{gamma}. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in HMECs. Our findings reveal a novel extra-telomeric organization of TIN2 associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of Biological andEnvironmental Research; National Institutes of Health Grants CA64786 andAG09909 and Training Grant AG00266, Department of Defense. Breast CancerResearch Program DAMD17-02-1-0438; Walther Cancer Institute WCI-100-114,Jim and Diane Robbers Foundation and Joyce Fox Jordan Cancer ResearchProgram. Purdue Cancer Center, California Breast Cancer Research Program88AV01 and 7FB0018, Danish Research Council and Novo NordiskFoundation
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 887187
- Report Number(s):
- LBNL-56791; JNCSAI; R&D Project: 443120; BnR: KP1104010; TRN: US200617%%591
- Journal Information:
- Journal of Cell Science, Vol. 118, Issue pt6; Related Information: Journal Publication Date: 03/01/2005; ISSN 0021-9533
- Country of Publication:
- United States
- Language:
- English
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