Document Detail


Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2.
MedLine Citation:
PMID:  15741234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 1gamma. 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.
Authors:
Patrick Kaminker; Cedric Plachot; Sahn-Ho Kim; Peter Chung; Danielle Crippen; Ole W Petersen; Mina J Bissell; Judith Campisi; Sophie A Lelièvre
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-01
Journal Detail:
Title:  Journal of cell science     Volume:  118     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-14     Completed Date:  2005-09-15     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1321-30     Citation Subset:  IM    
Affiliation:
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Breast / cytology*
Bromodeoxyuridine / pharmacology
Cell Culture Techniques / methods
Cell Differentiation
Cell Nucleus / metabolism*
Cell Proliferation
Cells, Cultured
Deoxyribonuclease I / metabolism
Deoxyribonucleases / metabolism
Epithelial Cells / cytology*,  metabolism
Heterochromatin / chemistry
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Ki-67 Antigen / biosynthesis
Microscopy, Fluorescence
Phenotype
Protein Structure, Tertiary
Retroviridae / genetics
Ribonuclease, Pancreatic / metabolism
Ribonucleases / metabolism
Telomere / metabolism,  ultrastructure
Telomere-Binding Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
AG00266/AG/NIA NIH HHS; AG09909/AG/NIA NIH HHS; CA64786/CA/NCI NIH HHS; R01 CA064786-05/CA/NCI NIH HHS; R37 AG009909-10/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Heterochromatin; 0/Ki-67 Antigen; 0/TINF2 protein, human; 0/Telomere-Binding Proteins; 59-14-3/Bromodeoxyuridine; EC 3.1.-/Deoxyribonucleases; EC 3.1.-/Ribonucleases; EC 3.1.21.1/Deoxyribonuclease I; EC 3.1.27.5/Ribonuclease, Pancreatic

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