MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene Are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct

Darwanto, Agus; Kitazawa, Riko; Mori, Kiyoshi; Kondo, Takeshi; Kitazawa, Sohei

doi:10.1267/ahc.08025

Cited by 15 publications

(11 citation statements)

References 21 publications

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“…We also showed that hMeCP2 expression in ECs can activate ISC activity. In mammals, MeCP2 was previously reported to regulate Cyclin D1 expression in developing rat gut (Darwanto et al, 2008), and it induces cell proliferation and growth of embryonic non-neuronal cells (Nagai et al, 2005) as well as prostate cancer cells (Bernard et al, 2006). Furthermore, MeCP2 has been reported to induce secretion of several growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and nerve growth factor (NGF) in the central nervous system (Schaevitz et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila

Lee

Kim

et al. 2011

Cell Struct. Funct.

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ABSTRACT. Recent studies have suggested the involvement of epigenetic factors such as methyl-CpG-binding protein-2 (MeCP2) in tumorigenesis. In addition, cancer may represent a stem cell-based disease, suggesting that understanding of stem cell regulation could provide valuable insights into the mechanisms of tumorigenesis. However, the function of epigenetic factors in stem cell regulation in adult tissues remains poorly understood. In the present study, we investigated the role of human MeCP2 (hMeCP2), a bridge factor linked to DNA modification and histone modification, in stem cell proliferation using adult Drosophila midgut, which appears to be an excellent model system to study stem cell biology. Results show that enterocyte (EC)-specific expression of hMeCP2 in adult midgut using an exogenous GAL4/UAS expression system induced intestinal stem cell (ISC) proliferation marked by staining with anti-phospho-histone H3 antibody and BrdU incorporation assays. In addition, hMeCP2 expression in ECs activated extracellular stress-response kinase signals in ISCs. Furthermore, expression of hMeCP2 modulated the distribution of heterochromatin protein-1 in ECs. Our data suggests the hypothesis that the expression of hMeCP2 in differentiated ECs stimulates ISC proliferation, implying a role of MeCP2 as a stem cell regulator.

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Section: Discussionmentioning

confidence: 99%

Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila

Lee

Kim

et al. 2011

Cell Struct. Funct.

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“…The significance of these in relation to gene expression was not investigated. Darwanto et al [54], however, showed an increase in the methylation of the CyclinD1 promoter during epididymal development, which appeared to be associated with a decreased expression of the gene. Nevertheless, the fact that DNA methylation may regulate the transcription of Panx1 may be important not only for epididymal function, but also in other tissues.…”

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 94%

Regulation of the Pannexin-1 Promoter in the Rat Epididymis1

Dufresne¹,

Cyr²

2014

Biology of Reproduction

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Pannexins (PANXs) are channel-forming proteins implicated in cellular communication through the secretion of biomolecules, such as ATP and glutamate. PANX1 and PANX3 are expressed in the male rat reproductive tract and their levels are regulated by androgens in the epididymis. There is currently no information on the regulation of the Panx1 promoter. The objective of the present study was to characterize the Panx1 promoter in order to understand its regulation in the epididymis. RNA ligase-mediated rapid amplification of cDNA ends identified three transcriptional start sites, at positions -443, -429, and -393. In silico analysis revealed that transcription was initiated downstream of binding sites for CREB and ETV4 transcription factors, in a CpG island context. To determine the importance of this region in gene transactivation, a 2-kb fragment of the promoter was cloned into a vector containing a luciferase reporter gene. Deletion constructs indicated that the highest transactivation levels were achieved with shorter constructs (-973 to -346 and -550 to -346). Electrophoretic mobility shift assay and supershifts indicated that both transcription factors were able to bind to the promoter region. Chromatin immunoprecipitation using rat caput epididymis cells confirmed the binding of ETV4 and CREB on the Panx1 promoter. Site mutation of either the ETV4 or CREB binding site decreased the transactivation of the reporter gene. Previous studies indicated that orchidectomy increased epididymal PANX1 levels. Likewise, we observed an increase in both ETV4 and CREB in orchidectomized rats. These results indicate that ETV4 and cAMP response elements play a role in the transcriptional regulation of Panx1 in the epididymis.

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“…15 However, recent studies using animal models have demonstrated that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and may function as both an activator and a repressor of the target genes. 16 MeCP2 mRNA has been examined by in situ hybridization in rats and is shown to be expressed in the ganglion cells and intestinal epithelium of the small intestine, Purkinje cells and other neurons in the brain, and in cells of the testis, 19 In humans, expression is also found in the colonic mucosa and colon cancers. 20 Neuronal expression found in rats is similar to the immunohistochemical findings revealed in the present study.…”

Section: Resultsmentioning

confidence: 99%

“…Selective neuronal staining was obtained in the cerebellar cortex and colonic Auerbach's plexus by taking into account that in rats MeCP2 mRNA expression is detected in these tissues and cells. 19 After incubation with the biotinylated second antibodies, immunoreactive products were either visualized by 3,3'-diaminobenzidine tetrahydrochloride (DAB) as brown, or by amino-ethyl carbazole (AEC) as red. For double immunolabeling, the sections were first incubated with an anti-large T monoclonal antibody which was visualized as blue by nitro-blue tetrazolium chloride/ 5-bromo-4-chloro-3'-indolylphosphatase (NBT/BCIP) via alkaline phosphatase reaction.…”

Section: Antibodiesmentioning

confidence: 99%

High expression of MeCP2 in JC virus-infected cells of progressive multifocal leukoencephalopathy brains

et al. 2011

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Mutations of the methyl CpG binding protein 2 (MeCP2) gene are a major cause of Rett syndrome. To investigate whether the expression of this gene was related to JC virus (JCV) infection, we examined brains of four progressive multifocal leukoencephalopathy (PML) patients. JCV infection was confirmed by immunohistochemical labeling with antibodies against JCV VP1, Agnoprotein and large T antigen. MeCP2 expression was examined by immunohistochemistry using a specific polyclonal antibody against MeCP2. In normal brains and uninfected cortices of PML brains, MeCP2 expression was observed in the nuclei of neurons, but not observed in glial and endothelial cell nuclei. In PML brains, however, intense immunolabeling was observed in abnormally enlarged glial nuclei of JCV-infected cells. The JCV infection was verified by immunolabeling against JCV VP1, Agnoprotein and large T antigen. Double immunolabeling using antibodies against large T antigen (visualized as blue) and MeCP2 (visualised as red) revealed purple JCV infected nuclei, which confirmed that the JCV infected nuclei expressed MeCP2. When we examined four MeCP2 related proteins, named as methyl CpG binding domains (MBD) 1, 2, 3, and 4, only MBD1 exhibited similar results to MeCP2. We conclude that MeCP2 is highly expressed in the JCV infected nuclei of PML brain and these results may provide a new insight into the mechanism which regulates the MeCP2 expression in glial cells by the infection of JCV.

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MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene Are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct

Cited by 15 publications

References 21 publications

Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila

Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila

Regulation of the Pannexin-1 Promoter in the Rat Epididymis1

High expression of MeCP2 in JC virus-infected cells of progressive multifocal leukoencephalopathy brains

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