scholarly journals Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents

2009 ◽  
Vol 202 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Elika Missaghian ◽  
Petra Kempná ◽  
Bernhard Dick ◽  
Andrea Hirsch ◽  
Rasoul Alikhani-Koupaei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Deacetylase Inhibitors ◽  
Cpg Island ◽  
Specific Expression ◽  
Tissue Specific ◽  
Adrenal Cells ◽  
Tissue Specific Expression ◽  
As Species ◽  
Species Specific

The CYP17A1 gene is the qualitative regulator of steroidogenesis. Depending on the presence or absence of CYP17 activities mineralocorticoids, glucocorticoids or adrenal androgens are produced. The expression of the CYP17A1 gene is tissue as well as species-specific. In contrast to humans, adrenals of rodents do not express the CYP17A1 gene and have therefore no P450c17 enzyme for cortisol production, but produce corticosterone. DNA methylation is involved in the tissue-specific silencing of the CYP17A1 gene in human placental JEG-3 cells. We investigated the role of DNA methylation for the tissue-specific expression of the CYP17A1 gene in rodents. Rats treated with the methyltransferase inhibitor 5-aza-deoxycytidine excreted the cortisol metabolite tetrahydrocortisol in their urine suggesting that treatment induced CYP17 expression and 17α-hydroxylase activity through demethylation. Accordingly, bisulfite modification experiments identified a methylated CpG island in the CYP17 promoter in DNA extracted from rat adrenals but not from testes. Both methyltransferase and histone deacetylase inhibitors induced the expression of the CYP17A1 gene in mouse adrenocortical Y1 cells which normally do not express CYP17, indicating that the expression of the mouse CYP17A1 gene is epigenetically controlled. The role of DNA methylation for CYP17 expression was further underlined by the finding that a reporter construct driven by the mouse −1041 bp CYP17 promoter was active in Y1 cells, thus excluding the lack of essential transcription factors for CYP17 expression in these adrenal cells.

scholarly journals Role of epigenetic modifications in normal globin gene regulation and butyrate-mediated induction of fetal hemoglobin

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3391-3397 ◽  
Author(s):  
Hassana Fathallah ◽  
Rona S. Weinberg ◽  
Yelena Galperin ◽  
Millicent Sutton ◽  
George F. Atweh
Keyword(s):  
Dna Methylation ◽  
Histone Deacetylase Inhibitors ◽  
Globin Gene ◽  
Strong Support ◽  
Fetal Hemoglobin ◽  
Epigenetic Modifications ◽  
Globin Genes ◽  
Specific Expression ◽  
Tissue Specific

Abstract Butyrate is a prototype of histone deacetylase inhibitors that is believed to reactivate silent genes by inducing epigenetic modifications. Although butyrate was shown to induce fetal hemoglobin (HbF) production in patients with hemoglobin disorders, the mechanism of this induction has not been fully elucidated. Our studies of the epigenetic configuration of the β-globin cluster suggest that DNA methylation and histone H3 acetylation are important for the regulation of developmental stage-specific expression of the β-like globin genes, whereas acetylation of both histones H3 and H4 seem to be important for the regulation of tissue-specific expression. These studies suggest that DNA methylation may be important for the silencing of the β-like globin genes in nonerythroid hematopoietic cells but may not be necessary for their silencing in nonhematopoietic cells. Furthermore, our studies demonstrate that butyrate exposure results in a true reversal of the normal developmental switch from γ- to β-globin expression. This is associated with increased histone acetylation and decreased DNA methylation of the γ-globin genes, with opposite changes in the β-globin gene. These studies provide strong support for the role of epigenetic modifications in the normal developmental and tissue-specific regulation of globin gene expression and in the butyrate-mediated pharmacologic induction of HbF production.

scholarly journals A Mouse Gene That Coordinates Epigenetic Controls and Transcriptional Interference To Achieve Tissue-Specific Expression

2007 ◽  
Vol 28 (2) ◽  
pp. 836-848 ◽  
Author(s):  
Alexandra C. Racanelli ◽  
Fiona B. Turner ◽  
Lin-Ying Xie ◽  
Shirley M. Taylor ◽  
Richard G. Moran
Keyword(s):  
Dna Methylation ◽  
Rna Polymerase Ii ◽  
Transcriptional Activity ◽  
Cpg Island ◽  
Specific Pattern ◽  
Transcriptional Elongation ◽  
Transcriptional Interference ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT The mouse fpgs gene uses two distantly placed promoters to produce functionally distinct isozymes in a tissue-specific pattern. We queried how the P1 and P2 promoters were differentially controlled. DNA methylation of the CpG-sparse P1 promoter occurred only in tissues not initiating transcription at this site. The P2 promoter, which was embedded in a CpG island, appeared open to transcription in all tissues by several criteria, including lack of DNA methylation, yet was used only in dividing tissues. The patterns of histone modifications over the two promoters were very different: over P1, histone activation marks (acetylated histones H3 and H4 and H3 trimethylated at K4) reflected transcriptional activity and apparently reinforced the effects of hypomethylated CpGs; over P2, these marks were present in tissues whether P2 was active, inactive, or engaged in assembly of futile initiation complexes. Since P1 transcriptional activity coexisted with silencing of P2, we sought the mechanism of this transcriptional interference. We found RNA polymerase II, phosphorylated in a pattern consistent with transcriptional elongation, and only minimal levels of initiation factors over P2 in liver. We concluded that mouse fpgs uses DNA methylation to control tissue-specific expression from a CpG-sparse promoter, which is dominant over a downstream promoter masked by promoter occlusion.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

scholarly journals Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1

2006 ◽  
Vol 26 (11) ◽  
pp. 4111-4121 ◽  
Author(s):  
Mohamad Zubair ◽  
Satoru Ishihara ◽  
Sanae Oka ◽  
Katsuzumi Okumura ◽  
Ken-ichirou Morohashi
Keyword(s):  
Adrenal Cortex ◽  
Binding Sites ◽  
Orphan Nuclear Receptor ◽  
Specific Expression ◽  
Steroidogenic Factor 1 ◽  
Tissue Specific ◽  
Adrenal Cells ◽  
Tissue Specific Expression ◽  
And Function ◽  
Intron 4

ABSTRACT The orphan nuclear receptor Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1) is essential for the proper development and function of reproductive and steroidogenic tissues. Although the expression of Ad4BP/SF-1 is specific for those tissues, the mechanisms underlying this tissue-specific expression remain unknown. In this study, we used transgenic mouse assays to examine the regulation of the tissue-specific expression of Ad4BP/SF-1. An investigation of the entire Ad4BP/SF-1 gene locus revealed a fetal adrenal enhancer (FAdE) in intron 4 containing highly conserved binding sites for Pbx-Prep, Pbx-Hox, and Ad4BP/SF-1. Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop. Indeed, a limited number of Hox family members were found to be expressed in the adrenal primordia. Whether a true fetal-type adrenal cortex is present in mice remained controversial, and this argument was complicated by the postnatal development of the so-called X zone. Using transgenic mice with lacZ driven by the FAdE, we clearly identified a fetal adrenal cortex in mice, and the X zone is the fetal adrenal cells accumulated at the juxtamedullary region after birth.

scholarly journals A 5-Methylcytosine Site of Growth Differentiation Factor 9 (GDF9) Gene Affects Its Tissue-Specific Expression in Sheep

Animals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 200
Author(s):  
Zhangyuan Pan ◽  
Xiangyu Wang ◽  
Ran Di ◽  
Qiuyue Liu ◽  
Wenping Hu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Methylation Level ◽  
Cpg Island ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Directed Mutation ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9 ◽  
Basal Transcriptional Activity

Growth differentiation factor 9 (GDF9) plays an important role in the early folliculogenesis of sheep. This study investigated the mRNA expression of ovine GDF9 in different tissues by real-time PCR. GDF9 exhibits significantly higher levels of expression (p < 0.01) in the ovary, relative to other tissues, indicating that its expression is tissue specific. To explore the regulatory mechanism of this tissue-specific expression, the methylation level of one CpG island (−1453 to −1854) of GDF9 promoter in ovary and heart was determined. In this region (−1987 to −1750), only the mC-4 site was present in the Sp4 binding site showed differential methylation between the heart and ovary; with increased (p < 0.01) methylation being observed in the heart. Additionally, the methylation level was negatively correlated with GDF9 mRNA expression (R = −0.75, p = 0.012), indicating that the methylation of this site plays an important role in transcriptional regulation of GDF9. The methylation effect of the mC-4 site was confirmed by using dual-luciferase. Site-directed mutation (methylation) of mC-4 site significantly reduced (p < 0.05) basal transcriptional activity of GDF9 promoter in oocytes. These results imply that methylation of GDF9 promoter CpG island mC-4 site may affect the binding of the Sp4 transcription factor to the GDF9 promoter region in sheep, thereby regulating GDF9 expression and resulting in a tissue-specific expression.

scholarly journals DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67925 ◽  
Author(s):  
Erling A. Hoivik ◽  
Solveig L. Witsoe ◽  
Inger R. Bergheim ◽  
Yunjian Xu ◽  
Ida Jakobsson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alternative Promoters ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

scholarly journals Root-Specific Expression of a Jacalin Lectin Family Protein Gene Requires a Transposable Element Sequence in the Promoter

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 550 ◽  
Author(s):  
Qiong Wu ◽  
Neil Smith ◽  
Daai Zhang ◽  
Changyong Zhou ◽  
Ming-Bo Wang
Keyword(s):  
Expression Pattern ◽  
Plant Defence ◽  
Plant Genome ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Family Protein ◽  
Lectin Family ◽  
Dna Demethylase

Transposable elements (TEs) are widespread in the plant genome and can impact on the expression of neighbouring genes. Our previous studies have identified a number of DNA demethylase-regulated defence-related genes that contain TE sequences in the promoter and show tissue-specific expression in Arabidopsis. In this study we investigated the role of the promoter TE insertions in the root-specific expression of a DNA demethylase-regulated gene, AT5G38550, encoding a Jacalin lectin family protein. Using a promoter:GUS fusion reporter gene approach, we first demonstrated that the full-length promoter fragment, carrying four TE sequences, contained the essential regulatory information required for root-specific expression and DNA demethylase regulation in Arabidopsis. By successive deletion of the four TE sequences, we showed that one of the four TE insertions, a 201-bp TE fragment of the hAT DNA transposon family, was required for root-specific expression: Deletion of this TE, but not the first two TE sequences, converted the root-specific expression pattern to a constitutive expression pattern in Arabidopsis plants. Our study provides an example indicating an important role of TE insertions in tissue-specific expression of plant defence-related genes.

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