Abstract:
:It has been hypothesized that protein factors may protect CpG islands from methyltransferase during development and that demethylation may involve protein-DNA interactions at demethylated sites. However, direct evidence has been lacking. In this study, demethylation at the EBNA-1 binding sites of the Epstein-Barr virus latent replication origin, oriP, was investigated by using human cells. Several novel findings are discussed. First, there are specific preferential demethylation sites within the oriP region. Second, the DNA sequence of oriP alone is not the target of an active demethylation process. Third, EBNA-1 binding is required for the site-specific demethylation in oriP. Interestingly, CpG sites adjacent to and between the EBNA-1 sites do not become demethylated. Fourth, demethylation of the first DNA strand in oriP at the EBNA-1 binding sites involves a passive (replication-dependent) mechanism. The second-strand demethylation appears to occur through an active mechanism. That is, EBNA-1 protein binding prevents the EBNA-1 binding sites from being remethylated after one round of DNA replication, and it appears that an active demethylase then demethylates these hemimethylated sites. This study provides clear evidence that protein binding specifies sites of DNA demethylation and provides insights into the sequence of steps and the mechanism of demethylation.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Hsieh CLdoi
10.1128/mcb.19.1.46subject
Has Abstractpub_date
1999-01-01 00:00:00pages
46-56issue
1eissn
0270-7306issn
1098-5549journal_volume
19pub_type
杂志文章abstract::To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bi...
journal_title:Molecular and cellular biology
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2001-11-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.7.2690
更新日期:1988-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2012-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.7.737
更新日期:1982-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.11.3722
更新日期:1986-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.13.4635-4647.2000
更新日期:2000-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2013-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1986-01-01 00:00:00
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更新日期:2011-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1988-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2004-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2003-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2003-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2006-08-01 00:00:00