scholarly journals Induction of IGFBP-1 Expression by cAMP Is Associated with Histone Acetylation Status of the Promoter Region in Human Endometrial Stromal Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5612-5621 ◽  
Author(s):  
Isao Tamura ◽  
Hiromi Asada ◽  
Ryo Maekawa ◽  
Manabu Tanabe ◽  
Lifa Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Stromal Cells ◽  
Promoter Region ◽  
Binding Protein ◽  
Methylation Status ◽  
Cell Types ◽  
Promoter Regions ◽  
Endometrial Stromal Cells ◽  
Acetylation Status

Abstract Many genes are up- or down-regulated in human endometrial stromal cells (ESCs) undergoing decidualization. IGF-binding protein-1 (IGFBP-1) and prolactin (PRL) are preferentially expressed during decidualization and are recognized as specific markers of decidualization. This study investigated the involvement of epigenetic mechanisms in the regulation of IGFBP-1 and PRL induction by decidualization in ESCs. ESCs isolated from the proliferative phase endometrium were incubated with cAMP to induce decidualization. Human dermal fibroblasts (HDFs) were used as a nonendometrial control. cAMP induced the expressions of both genes in ESCs but induced the expression of only PRL in HDFs. Histone acetylation levels of the IGFBP-1 promoter region evaluated by chromatin immunoprecipitation assay were higher in ESCs than in HDFs. The IGFBP-1 promoter regions in the two cell types showed similar levels of DNA hypomethylation. The histone acetylation levels and DNA methylation status of the PRL promoter and enhancer regions were similar in the two cell types. cAMP had no significant effects on the histone acetylation levels and DNA methylation status of the IGFBP-1 promoter and the PRL promoter and enhancer regions in ESCs. Cotreatment of HDF with cAMP and histone deacetylase inhibitors induced IGFBP-1 expression, which was accompanied by an increased histone acetylation level and recruitment of CCAAT/enhancer-binding protein-β to the promoter region. These results show that, during decidualization in ESCs, high histone acetylation status of the promoter regions of IGFBP-1 and PRL is associated with the induction of the IGFBP-1 and PRL genes by making the promoter regions accessible to transcriptional factors.

scholarly journals Importance of C/EBPβ Binding and Histone Acetylation Status in the Promoter Regions for Induction of IGFBP-1, PRL, and Mn-SOD by cAMP in Human Endometrial Stromal Cells

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 275-286 ◽  
Author(s):  
Isao Tamura ◽  
Shun Sato ◽  
Maki Okada ◽  
Manabu Tanabe ◽  
Lifa Lee ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Stromal Cells ◽  
Manganese Superoxide Dismutase ◽  
Mrna Levels ◽  
Epigenetic Mechanisms ◽  
Promoter Regions ◽  
Gene Expressions ◽  
Endometrial Stromal Cells ◽  
Acetylation Status ◽  
Igf Binding

Dynamic changes of gene expressions occur in human endometrial stromal cells (ESCs) during decidualization. CCAAT/enhancer-binding proteinβ (C/EBPβ) regulates the expression of a number of decidualization-related genes. In addition to transcription factors, it is important to know the role of epigenetic mechanisms, such as histone modifications in the regulation of decidualization-related genes. This study investigated the molecular and epigenetic mechanisms by which cAMP up-regulates the expression of IGF-binding protein-1 (IGFBP-1), prolactin (PRL), and manganese superoxide dismutase (Mn-SOD) in ESC. ESCs isolated from proliferative phase endometrium were incubated with cAMP to induce decidualization. IGFBP-1, PRL, and Mn-SOD mRNA expressions were determined by real-time RT-PCR. The C/EBPβ binding and histone modification status (acetylation of histone-H3 lysine-27 [H3K27ac]) in the promoter were examined by chromatin immunoprecipitation assay. Knockdowns of C/EBPβ were performed using the small interfering RNA method. cAMP induced mRNA expressions of IGFBP-1 and PRL accompanied by the increases in both C/EBPβ binding activities and H3K27ac levels in the promoters. The stimulatory effects of cAMP on mRNA levels and H3K27ac levels were completely abolished by C/EBPβ knockdown. cAMP increased Mn-SOD mRNA levels and C/EBPβ binding activities in the enhancer region. C/EBPβ knockdown inhibited Mn-SOD mRNA levels. The H3K27ac levels in the enhancer were high before cAMP stimulus but were not further increased by cAMP and were not inhibited by C/EBPβ knockdown. These results show that C/EBPβ regulates the expression of IGFBP-1 and PRL by altering the histone acetylation status of their promoters but differently regulates Mn-SOD gene expression in human ESC during decidualization.

Molecular inhibition of histone deacetylation results in major enhancement of the production of IL-1β in response to LPS

2006 ◽  
Vol 290 (3) ◽  
pp. E490-E493 ◽  
Author(s):  
Timothy A. Sato ◽  
Murray D. Mitchell
Keyword(s):  
Dna Methylation ◽  
Receptor Antagonist ◽  
Histone Acetylation ◽  
Trichostatin A ◽  
Cell Types ◽  
Causative Factor ◽  
Histone Deacetylation ◽  
The Other ◽  
Acetylation Status ◽  
Tnf Α

It has been postulated that the progression of human pregnancy to term is, in part, the result of a relative maternal Th2 immunological state. This can be activated in some cell types by modifying DNA methylation and histone acetylation status. We demonstrate that the molecular inhibition of histone deacetylation, using trichostatin A (TSA), in human choriodecidual explants leads to a massive increase in lipopolysaccharide (LPS)-stimulated IL-1β. The inhibition of histone deacetylation had no effect on LPS-stimulated TNF-α production or production of the other cytokines studied (IL-10, IL-1 receptor antagonist). The molecular inhibition of DNA methylation and histone deacetylation, using 5-aza-2′-deoxycytidine and TSA, respectively, in human choriodecidual explants also results in an increase in the basal production of TNF-α but not that of IL-1β. The differential response is unique, and the relative uncoupling of IL-1β and TNF-α responsiveness may have importance in other biological systems and provide new therapeutic targets for pathologies where upregulation of IL-1β is known to be a causative factor.

scholarly journals Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mai Mahmoud Shaker ◽  
Taghreed Abdelmoniem shalabi ◽  
Khalda said Amr
Keyword(s):  
Dna Methylation ◽  
Dna Sequences ◽  
Promoter Region ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Methylation Status ◽  
Control Group ◽  
Case Group ◽  
Methyl Radical ◽  
Fertile Women

Abstract Background DNA methylation is an epigenetic process for modifying transcription factors in various genes. Methylenetetrahydrofolate reductase (MTHFR) stimulates synthesis of methyl radical in the homocysteine cycle and delivers methyl groups needed in DNA methylation. Furthermore, numerous studies have linked gene polymorphisms of this enzyme with a larger risk of recurrent pregnancy loss (RPL), yet scarce information is available concerning the association between epigenetic deviations in this gene and RPL. Hypermethylation at precise DNA sequences can function as biomarkers for a diversity of diseases. We aimed by this study to evaluate the methylation status of the promoter region of MTHFR gene in women with RPL compared to healthy fertile women. It is a case–control study. Hundred RPL patients and hundred healthy fertile women with no history of RPL as controls were recruited. MTHFR C677T was assessed by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Quantitative evaluation of DNA methylation was performed by high-resolution melt analysis by real-time PCR. Results The median of percentage of MTHFR promoter methylation in RPL cases was 6.45 [0.74–100] vs. controls was 4.50 [0.60–91.7], P value < 0.001. In the case group, 57 hypermethylated and 43 normo-methylated among RPL patients vs. 40 hypermethylated and 60 normo-methylated among controls, P< 0.005. Frequency of T allele in C677T MTHFR gene among RPL patients was 29% vs. 23% among the control group; C allele vs. T allele: odds ratio (OR) = 1.367 (95% confidence interval (CI) 0.725–2.581). Conclusion Findings suggested a significant association between hypermethylation of the MTHFR promoter region in RPL patients compared to healthy fertile women.

Deficiency in Vitamin B12 and Ferritin Is Associated With Epigenetic Alterations in Cancer Patients  

2021 ◽  
Author(s):  
Khaled A. Elawdan ◽  
Sabah Farouk ◽  
Salah Araf ◽  
Hany Khalil
Keyword(s):  
Dna Methylation ◽  
Vitamin B12 ◽  
Cancer Patients ◽  
Promoter Region ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Promoter Regions ◽  
Methylation Sensitive Restriction Enzyme ◽  
Low Levels ◽  
Dna Methylation Analysis

Abstract Background: Cancer is the second-leading cause of death worldwide, caused by several mutations in DNA within the cells including epigenetic alteration. The epigenetic changes are external modifications to the DNA that switch “on” or “off” gene expression. The present study was conducted to investigate the epigenetic modifications and its correlation with the levels of vitamin B12 and ferritin in cancer patients with hepatocellular carcinoma (HCC), breast cancer (BC), lung cancer (LC), or colon cancer (CC). Methods and Results: A total of 200 blood samples were obtained from cancer patients and healthy individuals. The relative expression of DNA methyltransferases (DNMTs), Ten-Eleven translocation (TET), and methionine synthase (MS) was evaluated in patients with the normal level of vitamin B12/ferritin and patients with the deficient levels of them. DNA methylation within the promoter regions was investigated of each indicated genes using the methylation-sensitive restriction enzyme HpaII and bisulfite PCR. Interestingly, the expression of DNMT1, DNMT3a, and DNMT3b was increased in patients with low levels of vitamin B12 and ferritin, while the expression of MS, TET1, and TET3 was significantly decreased. DNA methylation analysis in patients with deficient levels of vitamin B12/ferritin showed a methylated-cytosine within the location 318/CG and 385/CG in the promoter region of TET1 and TET3, respectively. Moreover, the bisulfite PCR assay further confirmed the methylation changes in the promoter region of TET1 and TET3 at the indicated locations. Conclusion: These data indicate that the deficiency in vitamin B12 and ferritin in cancer patients plays a key role in the epigenetic exchanges during cancer development.

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