| Distinct and temporal roles of nucleosomal remodeling and histone deacetylation in the repression of the hTERT gene. | |
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MedLine Citation:
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PMID: 20053684 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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hTERT, the human telomerase reverse transcriptase, is highly expressed in stem cells and embryonic tissues but undetectable in most adult somatic cells. To understand its repression mechanisms in somatic cells, we investigated the endogenous hTERT gene regulation during differentiation of human leukemic HL60 cells. Our study revealed that silencing of the hTERT promoter was a biphasic process. Within 24 h after initiation of differentiation, hTERT mRNA expression decreased dramatically, accompanied by increased expression of Mad1 gene and disappearance of a nucleosome-free region at the hTERT core promoter. Subsequent to this early repression, nucleosomal remodeling continued at the promoter and downstream region for several days, as demonstrated by micrococcal nuclease and restriction enzyme accessibility assays. This later nucleosomal remodeling correlated with stable silencing of the hTERT promoter. Progressive changes of core histone modifications occurred throughout the entire differentiation process. Surprisingly, inhibition of histone deacetylation at the hTERT promoter did not prevent hTERT repression or nucleosomal deposition, indicating that nucleosomal deposition at the core promoter, but not histone deacetylation, was the cause of transcriptional repression. Our data also suggested that succeeding nucleosomal remodeling and histone deacetylation worked in parallel to establish the stable repressive status of hTERT gene in human somatic cells. |
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Authors:
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Shuwen Wang; Chunguang Hu; Jiyue Zhu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-06 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 21 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-26 Completed Date: 2010-07-26 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 821-32 Citation Subset: IM |
Affiliation:
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Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation* Cell Differentiation Epigenesis, Genetic Gene Expression Regulation* Gene Silencing HL-60 Cells Histones / metabolism* Humans Models, Biological Nucleosomes / metabolism* Promoter Regions, Genetic Reverse Transcriptase Polymerase Chain Reaction Telomerase / metabolism* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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GM-071725/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Histones; 0/Nucleosomes; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
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