Gene silencing in phenomena related to DNA repair

Mukai, Tsunehiro; Sekiguchi, Mutsuo

doi:10.1038/sj.onc.1206095

Cited by 18 publications

(11 citation statements)

References 85 publications

(89 reference statements)

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“…It is believed that methylated DNA sequences are bound by MBD proteins, such as MeCP2 and MBD2, and make complexes including histone deacetylase (HDAC) (Mukai and Sekiguchi, 2002). MeCP2 can bind to the methylated CpG island, and its binding is associated with deacetylation at the p14/p16 locus (Nguyen et al, 2001).…”

Section: Involvement Of Methyl-cpg Binding Proteins In Mgmt Silencingmentioning

confidence: 99%

“…The silencing of MGMT is also related to methylation of the 5 0 flanking region of the gene (von Wronski et al, 1992;Costello et al, 1994a;Danam et al, 1999;Herfarth et al, 1999). Methyl-CpG binding (MBD) proteins, such as MeCP2 and MBD2, bind to the aberrant methylated sequences and recruit histone deacetylase complex, leading to alteration of chromatin configuration, to prevent binding of the transcription factors Mukai and Sekiguchi, 2002). The importance of post-transcriptional histone modifications in epigenetic gene regulation, such as acetylation and methylation at amino-termini, has been emerging from recent studies (Jenuwein and Allis, 2001;Heard et al, 2001;Xin et al, 2001;Boggs et al, 2002;Peters et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer

Nakagawachi¹,

Soejima²,

et al. 2003

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9Biomolecular Engineering Research Institute (BERI), Japan O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter region; however, how the epigenetic silencing mechanism works, as it relates to hypermethylation, was still unclear. To understand the mechanism, we examined the detailed methylation status of the whole island with bisulfitesequencing in 19 MGMT non-expressed cancer cell lines. We found two highly methylated regions in the island. One was upstream of exon 1, including minimal promoter, and the other was downstream, including enhancer. Reporter gene assay showed that methylation of both the upstream and downstream regions suppressed luciferase activity drastically. Chromatin immunoprecipitation assay revealed that histone H3 lysine 9 was hypermethylated throughout the island in the MGMT negative line, whereas acetylation on H3 and H4 and methylation on H3 lysine 4 were at significantly high levels outside the minimal promoter in the MGMT-expressed line. Furthermore, MeCP2 preferentially bound to the CpG-methylated island in the MGMT negative line. Given these results, we propose a model for gene silencing of MGMT that is dependent on the epigenetic state in cancer.

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Section: Involvement Of Methyl-cpg Binding Proteins In Mgmt Silencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer

Nakagawachi¹,

Soejima²,

et al. 2003

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“…In addition to that, the epigenetic inactivation may affect all molecular mechanisms involved in cell immortalization and transformation. Last but not least, it seems that epigenetic changes are among the several early steps in carcinogenesis (Mukai and Sekiguchi, 2002).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation analysis of the tumor suppressor gene CDKN2B in Brazilian leukemia patients

et al. 2008

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The aim of this work was to evaluate the methylation profile of the p15 (CDKN2B) gene in Brazilian patients with leukemia and to correlate the CDKN2B gene expression with the percentage of methylated CpG dinucleotides in its promoter region. Thirty-one samples from six patients with acute lymphocytic leukemia (ALL), four with chronic myeloid leukemia (CML), and 21 with acute myeloid leukemia (AML) were evaluated by MSP (Methylation-Specific PCR). The CDKN2B gene was found to be methylated in four (67%) of the six ALL samples and in 16 (76%) of the 21 AML samples, but in none of the four CML samples analyzed. We observed a correlation between the CDKN2B mRNA expression (RT-PCR) and the percentage of methylated CpG dinucleotides. Therefore, this study in Brazilian patients confirms that the CDKN2B gene is methylated in the majority of leukemia patients.

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“…Epigenetic modification of chromatin is considered to be a fundamental and important mechanism involved in the generation and maintenance of the imprinted states of imprinted genes (8). Epigenetic modifications, such as DNA methylation, modifications of histones, and the organization of nucleosomes, have been regarded as important because they have essential and general functions, not only for imprinted genes but also in the regulation of all genes (19,26,28,45).…”

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confidence: 99%

The Mouse Murr1 Gene Is Imprinted in the Adult Brain, Presumably Due to Transcriptional Interference by the Antisense-Oriented U2af1-rs1 Gene

Wang¹,

Joh²,

Masuko³

et al. 2004

Molecular and Cellular Biology

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The mouse Murr1 gene contains an imprinted gene, U2af1-rs1, in its first intron. U2af1-rs1 shows paternal allele-specific expression and is transcribed in the direction opposite to that of the Murr1 gene. In contrast to a previous report of biallelic expression of Murr1 in neonatal mice, we have found that the maternal allele is expressed predominantly in the adult brain and also preferentially in other adult tissues. This maternalpredominant expression is not observed in embryonic and neonatal brains. In situ hybridization experiments that used the adult brain indicated that Murr1 gene was maternally expressed in neuronal cells in all regions of the brain. We analyzed the developmental change in the expression levels of both Murr1 and U2af1-rs1 in the brain and liver, and we propose that the maternal-predominant expression of Murr1 results from transcriptional interference of the gene by U2af1-rs1 through the Murr1 promoter region.

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Gene silencing in phenomena related to DNA repair

Cited by 18 publications

References 85 publications

Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer

Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer

DNA methylation analysis of the tumor suppressor gene CDKN2B in Brazilian leukemia patients

The Mouse Murr1 Gene Is Imprinted in the Adult Brain, Presumably Due to Transcriptional Interference by the Antisense-Oriented U2af1-rs1 Gene

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