CpG methylation remodels chromatin structure in vitro

Davey, Colin S.; Pennings, Sari; Allan, James

doi:10.1006/jmbi.1997.0899

Cited by 95 publications

(63 citation statements)

References 66 publications

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“…Hypermethylation may occur within CpG islands or at isolated CpG sites, and in either case may be correlated with transcriptional inactivation. Transcriptional repression by hypermethylation is typically chromatindependent and may be mediated by the recruitment of histone deacetylase (Nan et al, 1998) or other mechanisms, including unfavorable nucleosomal positioning (Davey et al, 1997).…”

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confidence: 99%

Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells

2000

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We investigated the mechanism of retinoic acid receptor (RAR) b2 gene silencing in breast cancer cells. Transfection experiments indicated that MCF-7 cells transactivate an exogenous b2 promoter (71470/+156) to the same extent as MTSV1.7 breast epithelial cells, which express endogenous RARb2. This was true even in the context of replicated chromatin, suggesting a cisacting rather than a trans-acting defect. Cytosine methylation, a cis-acting DNA modi®cation, has been implicated in RARb2 silencing in cancer cells. Upon bisul®te genomic sequencing, we found that 3 CpG sites in the b2 RARE region were variably methylated in MCF-7 cells but were not methylated in MTSV1.7 cells or in 2 MDA-MB-231 subclones that di ered in RARb2 expression (high in clone A2, low in clone A4). However, the 5'-UTR region was hypermethylated in clone A4 relative to clone A2 cells. Following 5-azacytidine treatment, RA and trichostatin A markedly induced RARb2 expression in MCF-7 cells but not in MDA-MB-231 clone A4 cells. A b2 RARE reporter construct in which the methylation-susceptible cytosines in the sense strand were replaced by thymine displayed marked loss of activity in a replicated chromatin-dependent manner. We conclude that cytosine methylation contributes to RARb2 gene silencing in MCF-7 cells and that methylation of the RARE region may be particularly important.

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confidence: 99%

Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells

2000

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“…The MAT2A promoter contains a large G+C rich domain characteristic of housekeeping genes [9,10]. These CpG islands are usually free of methylated cytosines, but if methylated the gene is rendered inactive [10,28]. Our observations demonstrate that MAT1A and MAT2A display a methylation pattern which closely correlates with their expression pro®le.…”

Section: Resultsmentioning

confidence: 59%

“…Lower panels show the expression of either MAT1A (A) or MAT2A (B) in the di erent rat tissues as analyzed by Northern blotting. both MAT genes it is known that the pattern of DNA methylation can in¯uence the chromatin structure formed around a gene [10,11,28] and that the inactive chromatin structure associated with DNA methylation is important for the loss of transcriptional activity [12].…”

Section: Resultsmentioning

confidence: 99%

“…Several mechanisms have been proposed, they included the direct modulation of chromatin structure by DNA methylation [28], the interference with binding of transcription factors [10], and the implication of methylated-DNA binding proteins that would induce the formation of an inactive chromatin structure [10,11]. However the molecular link between methyl groups on the DNA and the modi®cation of chromatin remained elusive.…”

Section: Resultsmentioning

confidence: 99%

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DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Torres

López-Rodas

Latasa

et al. 2000

The International Journal of Biochemistry & Cell Biology

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Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet). In mammals MAT activity derives from two separate genes which display a tissue-speci®c pattern of expression. While MAT1A is expressed only in the adult liver, MAT2A is expressed in non-hepatic tissues. The mechanisms behind the selective expression of these two genes are not fully understood. In the present report we have evaluated MAT1A and MAT2A methylation in liver and in other tissues, such as kidney, by methylationsensitive restriction enzyme digestion of genomic DNA. Our data indicate that MAT1A is hypomethylated in liver and hypermethylated in non-expressing tissues. The opposite situation is found for MAT2A. Additionally, histones associated to MAT1A and MAT2A genes showed enhanced levels of acetylation in expressing tissues (two-fold for MAT1A and 3.5-fold for MAT2A liver and kidney respectively). These observations support a role for chromatin structure and its modi®cation in the tissue-speci®c expression of both MAT genes. #

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“…Z-DNA formation might act by absorbing the negative supercoils released by removal of the nucleosome(s) at the promoter region. In addition, it may play a more active role in removing or repositioning overlying nucleosomes because of the fact that formation of nucleosomes on Z-DNA or methylated d(CG) dinucleotide repeats is highly disfavored (17)(18)(19)(20)(21)(22). In both scenarios, an ''open'' chromatin region is stabilized by the DNA conformational change (3).…”

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confidence: 99%

Characterization of Z-DNA as a nucleosome-boundary element in yeastSaccharomyces cerevisiae

Wong

Chen

Kwon

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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In this article, the effect of a d(CG) DNA dinucleotide repeat sequence on RNA polymerase II transcription is examined in yeast Saccharomyces cerevisiae. Our previous report shows that a d(CG)n dinucleotide repeat sequence located proximally upstream of the TATA box enhances transcription from a minimal CYC1 promoter in a manner that depends on its surrounding negative supercoiling. Here, we demonstrate that the d(CG)9 repeat sequence stimulates gene activity by forming a Z-DNA secondary structure. Furthermore, the extent of transcriptional enhancement by Z-DNA is promoter-specific and determined by its separation distance relative to the TATA box. The stimulatory effect exerted by promoter proximal Z-DNA is not affected by helical phasing relative to the TATA box, suggesting that Z-DNA effects transcription without interacting with the general transcription machinery by loopingout the intervening DNA. A nucleosome-scanning assay reveals that the d(CG)9 repeat sequence in the Z conformation blocks nucleosome formation, and it is found in the linker DNA with two flanking nucleosomes. This result suggests that Z-DNA formation proximally upstream of a promoter is sufficient to demarcate the boundaries of its neighboring nucleosomes, which produces transcriptionally favorable locations for the TATA box near the nucleosomal DNA-entry site and at dyad positions on the nucleosome. These findings suggest that Z-DNA formation in chromatin is a part of the ''genomic code'' for nucleosome positioning in vivo.chromatin remodeling ͉ promoter ͉ transcription ͉ nucleosome positioning

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CpG methylation remodels chromatin structure in vitro

Cited by 95 publications

References 66 publications

Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells

Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells

DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Characterization of Z-DNA as a nucleosome-boundary element in yeastSaccharomyces cerevisiae

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