DNA Binding Selectivity of MeCP2 Due to a Requirement for A/T Sequences Adjacent to Methyl-CpG

Klose, Robert J.; Sarraf, Shireen A.; Schmiedeberg, Lars; McDermott, Suzanne M.; Stancheva, Irina; Bird, Adrian

doi:10.1016/j.molcel.2005.07.021

Cited by 307 publications

(312 citation statements)

References 65 publications

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“…By analyzing Kaiso-binding sites in HEK293T cells, Ruzov et al found that Kaiso associates with methylated CpGs but not CTGCNA sites, and importantly, their data show that only the methylated DNA-binding function of Kaiso is required in early Xenopus laevis development [37]. It should be noted that binding of MBPs to methylated DNA appears to be sequence-specific: additional DNA sequence surrounding the CpG site(s) is important [38,39].…”

Section: Discussionmentioning

confidence: 99%

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

et al. 2011

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Postnatal growth and regeneration of skeletal muscle are carried out mainly by satellite cells, which, upon stimulation, begin to express myogenin (Myog), the critical determinant of myogenic differentiation. DNA methylation status has been associated with the expression of Myog, but the causative mechanism remains almost unknown. Here, we report that the level of CIBZ, a methyl-CpG-binding protein, decreases upon myogenic differentiation of satellitederived C2C12 cells, and during skeletal muscle regeneration in mice. We present data showing that the loss of CIBZ promotes myogenic differentiation, whereas exogenous expression of CIBZ impairs it, in cultured cells. CIBZ binds to a Myog promoter-proximal region and inhibits Myog transcription in a methylation-dependent manner. These data suggest that the suppression of myogenic differentiation by CIBZ is dependent, at least in part, on the regulation of Myog. Our data show that the methylation status of this proximal Myog promoter inversely correlates with Myog transcription in cells and tissues, and during postnatal growth of skeletal muscle. Notably, induction of Myog transcription by CIBZ suppression is independent of the demethylation of CpG sites in the Myog promoter. These observations provide the first reported molecular mechanism illustrating how Myog transcription is coordinately regulated by a methyl-CpG-binding protein and the methylation status of the proximal Myog promoter.

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Section: Discussionmentioning

confidence: 99%

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

et al. 2011

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“…This family of proteins consists of five well-characterised members (MeCP2, MBD1, MBD2, MBD3 and MBD4) (Esteller, 2005a). MBD proteins are associated with hypermethylated CpG island promoters of tumour-suppressor genes and their transcriptional silencing (Esteller, 2005a), showing remarkable specificity in vitro and in vivo Klose et al, 2005).…”

Section: Estellermentioning

confidence: 99%

Epigenetics provides a new generation of oncogenes and tumour-suppressor genes

2006

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Cancer is nowadays recognised as a genetic and epigenetic disease. Much effort has been devoted in the last 30 years to the elucidation of the 'classical' oncogenes and tumour-suppressor genes involved in malignant cell transformation. However, since the acceptance that major disruption of DNA methylation, histone modification and chromatin compartments are a common hallmark of human cancer, epigenetics has come to the fore in cancer research. One piece is still missing from the story: are the epigenetic genes themselves driving forces on the road to tumorigenesis? We are in the early stages of finding the answer, and the data are beginning to appear: knockout mice defective in DNA methyltransferases, methyl-CpG-binding proteins and histone methyltransferases strongly affect the risk of cancer onset; somatic mutations, homozygous deletions and methylation-associated silencing of histone acetyltransferases, histone methyltransferases and chromatin remodelling factors are being found in human tumours; and the first cancer-prone families arising from germline mutations in epigenetic genes, such as hSNF5/INI1, have been described. Even more importantly, all these 'new' oncogenes and tumour-suppressor genes provide novel molecular targets for designed therapies, and the first DNA-demethylating agents and inhibitors of histone deacetylases are reaching the bedside of patients with haematological malignancies.

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“…No apparent difference in MECP2 binding activity to CpG 3 was observed between methylated and unmethylated states. It has been reported that an [A/T] ≥4 , a sequence adjacent to methyl‐CpG, is necessary for high‐affinity MECP2 binding 12. Four A/T bases were observed within the 3 bases of CpG1 and within 4 bases of CpG3, whereas CpG2 contained no A/T run.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II

Takeda

Demura

Wang

et al. 2018

JAHA

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Background DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene (CYP11B2).Methods and Results DNA methylation of CYP11B2 was analyzed in aldosterone‐producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the CYP11B2 promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of CYP11B2. Methylation of the CYP11B2 promoter fused to a reporter gene decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1), and NURR1 (NR4A2) diminished their DNA‐binding activity. A methylated‐CpG‐binding protein MECP2 interacted directly with the methylated CYP11B2 promoter. In rats, low salt intake led to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with angiotensin II type 1 receptor antagonist decreased CYP11B2 expression and led to DNA hypermethylation.Conclusions DNA demethylation may switch the phenotype of CYP11B2 expression from an inactive to an active state and regulate aldosterone biosynthesis.

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DNA Binding Selectivity of MeCP2 Due to a Requirement for A/T Sequences Adjacent to Methyl-CpG

Cited by 307 publications

References 65 publications

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

Epigenetics provides a new generation of oncogenes and tumour-suppressor genes

Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II

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