Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies showed that progesterone receptor (PR), one of the hormone receptor superfamily, was only connected with the sex-correlated cancers such as breast cancer, endometrial cancer, prostate cancer, etc. This article deals with the PR gene in leukemia. We investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in three leukemia cancer cell lines using methylation-specific polymerase chain reaction (MSP-PCR) and reverse transcription-PCR. The correlation of PR methylation and expression together with DNA methyltransferase (DNMT1) was further studied. We found that DNMT1 is required to maintain CpG methylation and aberrant gene silencing of PR gene in human leukemia cancer cells. The activity of 5-aza-2'-deoxycytidine in demethylation and gene reactivation may be through depleting cellular DNMT1 levels. In addition, extensive methylation of PRA and PRB was also observed in leukemia samples. Our results suggest that PR CpG island aberrant hypermethylation could be one molecular and genetic alteration in leukemia.
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PMID:Progesterone receptor gene inactivation and CpG island hypermethylation in human leukemia cancer cells. 1517 46

The functional interaction of progesterone receptor (PR) isoforms PRA and PRB regulates myometrial transition from the resting state to excitation-contraction to initiate parturition. However, the regulatory mechanisms responsible for maintenance and functional alteration of the PRA and PRB expression levels during human pregnancy and term labor, respectively, remain unknown. Therefore, this study was designed to investigate whether and how epigenetic DNA modifications, specifically methylations, at the PRs' promoter regions contribute to the differential expression of PRA and PRB in laboring term myometrium of humans. Comparative analysis of PRA and PRB messenger RNA (mRNA) expression levels and accompanying changes in their promoters' methylation status was carried out using human myometrial samples from women undergoing singleton, term deliveries by cesarean section, either in the absence of labor (designated as NIL for not-in-labor) or in active labor (designated as IL for in labor). The PRA gene expression was shown to be elevated significantly during labor, while PRB gene expression was unaltered, and this differential expression was accompanied by decreased DNA methylation at the PRA promoter and not at the PRB promoter. In addition, labor-related decreased mRNA expression of the DNA methyltransferase (DNMT) family members DNMT1 and DNMT3a was found, however whether the increased expression of DNMTs directly supports the functional withdrawal of progesterone needs further investigation. Collectively, these data indicate that DNA methylation might represent an important epigenetic mechanism of labor-related differential expression of PRs, thereby mediating the biological process of functional PR withdrawal at term for parturition.
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PMID:Decreased DNA Methylations at the Progesterone Receptor Promoter A Induce Functional Progesterone Withdrawal in Human Parturition. 2440 75