Alterations in the Chromatin Structure of the Distal Promoter Region of the Bovine Oxytocin Gene Correlate with Ovarian Expression

Kascheike, Bernd; Ivell, Richard; Walther, Norbert

doi:10.1089/dna.1997.16.1237

Cited by 16 publications

(9 citation statements)

References 47 publications

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“…While RAR␣ is ubiquitously expressed in adult tissues, RAR␤ and RAR␥ expression is much more restricted, suggesting a mechanism by which tissue-specific expression of retinoid target genes may be achieved through expression of different RARs [42,43]. Our observation that RA represses FSHR expression strongly supports the conclusion that retinoid signals may indeed be involved in the stagespecific regulation of FSHR gene expression.…”

Section: Discussionsupporting

confidence: 75%

Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element1

Xing¹,

Sairam²

2002

Biology of Reproduction

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The FSH receptor (FSHR) and retinoid receptors are critical regulators of gonadal function. Unlike the latter, the FSH receptors are expressed exclusively in ovarian granulosa and testicular Sertoli cells in a developmental fashion. Toward understanding the nature of various transcription factors that direct a tissue- and stage-specific expression of the FSHR gene, we have studied FP4, one of the two footprinting regions (FP3 and FP4) mapped at -241 to -269 and -284 to -303, respectively, upstream of the transcription start site of the ovine FSHR gene. Gel mobility shift assays with FP4 probe revealed two sequence-specific DNA-protein complexes in the presence of nuclear extracts from two immortal gonadal cell lines. Antibody supershift assays demonstrated that retinoic acid receptor (RAR) was involved in the complex 1 whereas steroidogenic factor-1 (SF-1) was present in the complex 2. Mutation studies revealed that DNA binding sites for RAR and SF-1 were overlapping each other within a 19-base pair length of nucleotide sequence of FP4, and a mutation in the half RAR binding site seriously affected SF-1 binding. Reporter assays showed that FP4 conferred SF-1 transactivation as well as RAR-mediated, ligand-dependent repression. Overexpression of SF-1 in a transformed Sertoli cell line partially overcame RAR-mediated suppression. For the first time, our studies reveal a direct retinoid modulation of the gonadotropin receptor promoter and suggest a mechanism by which activators and repressors compete for composite elements providing antagonistic pathways that could modulate the expression of FSHR.

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Section: Discussionsupporting

confidence: 75%

Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element1

Xing¹,

Sairam²

2002

Biology of Reproduction

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“…It has also been reported for the bovine and ovine placenta that high-level expression coincides with hypomethylation of the main placental promoter [12][13][14]. Also in the case of the bovine oxytocin locus, it has been found that promoter methylation and chromatin compaction correlate with up-and down-regulation of gene expression in differentiating bovine granulosa cells [15].…”

Section: Introductionmentioning

confidence: 79%

DNA Methylation Is Not Involved in Preovulatory Down-Regulation of CYP11A1, HSD3B1, and CYP19A1 in Bovine Follicles but May Have a Role in Permanent Silencing of CYP19A1 in Large Granulosa Lutein Cells1

Vanselow

Spitschak

Nimz

et al. 2010

Biology of Reproduction

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The luteinizing hormone-induced morphological and physiological reorganization of the bovine follicle is preceded by a profound and well-orchestrated modulation of gene expression. In the present study, the cell type-specific methylation profiles of CYP11A1, HSD3B1, and CYP19A1, genes that encode key enzymes of steroid hormone biosynthesis, were analyzed to elucidate whether epigenetic parameters such as DNA methylation might be involved in gene regulation during luteinization. Transcript abundance and DNA methylation levels were determined in granulosa and theca of large dominant and late preovulatory follicles and in large granulosa lutein cells isolated from corpora lutea cyclica and graviditatis. Levels of the steroid hormones progesterone and estradiol-17beta were monitored to assess the physiological status of individual follicles. From our results, we conclude that (1) individual, even closely neighboring, CpG dinucleotides can show very different methylation levels; (2) proximal (<300 base pair [bp] from the respective transcription start sites) but not distal CpGs show cell type-specific methylation levels; (3) higher methylation levels suggestively preclude high levels of gene expression; (4) DNA methylation is not involved in the transient (HSD3B1 and CYP11A1) respectively permanent (CYP19A1) down-regulation of gene expression in late preovulatory follicles; and (5) DNA methylation may have a role in the permanent shutdown of promoter 2-directed CYP19A1 expression in large (granulosa derived) lutein cells.

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“…However, there is evidence that OXT DNA methylation is associated with OXT expression in bovine cells. Bovine cells that express OXT have low levels of promoter (28). It is currently unclear how exogenous and endogenous factors may impact DNA methylation of the OXT gene.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic modification ofOXTand human sociability

Haas

Filkowski

Cochran

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Across many mammalian species there exist genetic and biological systems that facilitate the tendency to be social. Oxytocin is a neuropeptide involved in social-approach behaviors in humans and others mammals. Although there exists a large, mounting body of evidence showing that oxytocin signaling genes are associated with human sociability, very little is currently known regarding the way the structural gene for oxytocin (OXT) confers individual differences in human sociability. In this study, we undertook a comprehensive approach to investigate the association between epigenetic modification of OXT via DNA methylation, and overt measures of social processing, including self-report, behavior, and brain function and structure. Genetic data were collected via saliva samples and analyzed to target and quantify DNA methylation across the promoter region of OXT. We observed a consistent pattern of results across sociability measures. People that exhibit lower OXT DNA methylation (presumably linked to higher OXT expression) display more secure attachment styles, improved ability to recognize emotional facial expressions, greater superior temporal sulcus activity during two social-cognitive functional MRI tasks, and larger fusiform gyrus gray matter volume than people that exhibit higher OXT DNA methylation. These findings provide empirical evidence that epigenetic modification of OXT is linked to several overt measures of sociability in humans and serve to advance progress in translational social neuroscience research toward a better understanding of the evolutionary and genetic basis of normal and abnormal human sociability.ociability is a central feature of the human species. Through one perspective, the complex array of human social-cognition and behavior serves to differentiate humans from other animals. However, there exist several core elemental components of the human sociobiological system that are present across many animal species, which may have remained relatively conserved throughout recent evolutionary history (1). Elucidating the genetic and biological substrates of social behavior serves to advance the way basic human nature is understood and improves the way genetic and biological markers can be used to prevent, diagnose, and treat people with impairments in social cognition and behavior.Oxytocin is a neurohypophysial peptide synthesized in the hypothalamus in the brain, linked to a wide range of social behaviors in humans and other mammals. Administration of oxytocin in humans is associated with changes in social-approach behaviors, such as trust (2) and personal proximity (3). This evidence has motivated the search for genes within the oxytocin system that confer individual differences in social behavior and cognition. A burgeoning body of evidence highlights the role of several key genes within the oxytocin signaling pathway linked to sociability, including the oxytocin receptor gene (OXTR), CD38, and the structural gene for oxytocin (OXT) (4). Although mounting data strongly support the role of ...

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Alterations in the Chromatin Structure of the Distal Promoter Region of the Bovine Oxytocin Gene Correlate with Ovarian Expression

Cited by 16 publications

References 47 publications

Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element1

Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element1

DNA Methylation Is Not Involved in Preovulatory Down-Regulation of CYP11A1, HSD3B1, and CYP19A1 in Bovine Follicles but May Have a Role in Permanent Silencing of CYP19A1 in Large Granulosa Lutein Cells1

Epigenetic modification ofOXTand human sociability

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