Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in normal cells. At present, it is also clear that DNA methylation forms an important part of the normal cell-regulatory processes that govern gene transcription. Methylation, targeted at CpG islands, is an important part of the mechanisms that govern X-chromosome inactivation; it is also essential for the maintenance of imprinted genes and, at least in some cases, is critical in determining the cell-type-specific expression patterns of genes. Study of these examples will be important in identifying the mechanisms that control targeting of DNA methylation and how these processes are disrupted during disease pathogenesis.
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PMID:Control of gene expression by CpG island methylation in normal cells. 1550 22

Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumour suppressor gene. The causative gene for the remaining meningiomas is unknown. Previous studies have shown that these tumours have no recurrent karyotypic abnormalities. They differ from their NF2-related counterparts in that they are more often of the meningothelial subtype and are located preferentially in the anterior skull base. To gain more insight into the aetiology of these tumours, we studied genetic and epigenetic alterations in 25 meningiomas without NF2 involvement. We first established a genome-wide allelotype using 3 microsatellite markers per chromosome arm. Loss of heterozygosity (LOH) was detected at a low frequency and no indication for the location of putative tumour suppressor genes could be established. We next screened the subtelomeric regions by using 2-3 polymorphic markers close to each telomere. Again no evidence for LOH of a particular chromosome arm was obtained, and no LOH was found in the genomic regions containing the NF2-related ERM family members ezrin and radixin, DAL-1, protein 4.1R, and TSLC1. Mutations in the X-chromosome based family member, moesin, were analysed by SSCP and were not detected. Microsatellite instability was studied using 6 commonly used markers but none of these was altered in any meningioma. Methylation was detected in 5 of 16 genes (NF2, p14(ARF), CDH1, BRCA1, RB1) previously shown to be silenced in a variety of tumour types. However, methylation percentages for these genes were generally higher in a group of NF2-related meningiomas, with the exception of the BRCA1 gene. The NF2 gene was methylated in only 1 of 21 tumours. In conclusion, meningiomas with an intact NF2 gene have a normal karyotype and no obvious genetic or epigenetic aberrations, suggesting that the gene(s) involved in the pathogenesis of these tumours are altered by smaller events than can be detected with the techniques used in our study.
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PMID:Lack of genetic and epigenetic changes in meningiomas without NF2 loss. 1635 69

DNA methylation regulates many cellular processes, including embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting and chromosome stability. DNA methyltransferases establish and maintain the presence of 5-methylcytosine (5mC), and ten-eleven translocation cytosine dioxygenases (TETs) oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which can be removed by base excision repair (BER) proteins. Multiple forms of DNA methylation are recognised by methyl-CpG binding proteins (MeCPs), which play vital roles in chromatin-based transcriptional regulation, DNA repair and replication. Accordingly, defects in DNA methylation and its mediators may cause silencing of tumour suppressor genes and misregulation of multiple cell cycles, DNA repair and chromosome stability genes, and hence contribute to genome instability in various human diseases, including cancer. Thus, understanding functional genetic mutations and aberrant expression of these DNA methylation mediators is critical to deciphering the crosstalk between concurrent genetic and epigenetic alterations in specific cancer types and to the development of new therapeutic strategies.
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PMID:DNA methylation, its mediators and genome integrity. 2589 67