Localization of promoter elements in the human mu-opioid receptor gene and regulation by DNA methylation

Andria, Matthew L.; Simon, Eric J.

doi:10.1016/s0169-328x(99)00126-6

Cited by 35 publications

(28 citation statements)

References 65 publications

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“…For example, nerve cells lines have multiple transcription initiation sites (TIS) as has been shown by various studies [Wang et al, 1994;Liang et al, 1995;Choe et al, 1998;Ko et al, 1998;Wendel and Hoehe, 1998;Andria and Simon, 1999;Xu and Carr, 2000;Choi et al, 2005]. However, in lymphocytes, there is only one transcription initiation site located at 110 bp upstream of the translation start codon as shown by data from our recent investigations .…”

supporting

confidence: 53%

“…It is likely that a dissimilar regulatory mechanism for the expression of the MOR exists in lymphocytes. For example, as compared with the multiple transcription initiation sites found in rodent brain cells and in human neuroblastoma SK-N-SH cells, only one initiation site has been detected in lymphocytes, which might be the direct reason accounting for the lower number of copies of the MOR transcripts in lymphocytes and the difficulty in detection of MOR mRNA in lymphocytes [Min et al, 1994;Liang et al, 1995;Andria and Simon, 1999;Madden et al, 2001;Wei et al, 2005]. In addition, two cis-acting elements, namely Sp1 and YY1 boxes, were predicted to reside immediately upstream of the translation start site of the MOR gene in CEM x174 cells, and were identified as critical for controlling promoter activity of the MOR gene in lymphocytes .…”

Section: Discussionmentioning

confidence: 99%

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The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes

Liu

Wang

et al. 2007

J of Cellular Biochemistry

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Although previous studies have shown that the mechanism of the lymphocyte mu opioid receptor (MOR) gene expression was distinctly different from that in the central nervous system, and is involved in several disparate aspects of the immune response, its precise molecular mechanism is still undefined. In this study, we analyzed the proximal promoter region of the MOR gene in lymphocytes to identify the influences of potential trans-acting factors in activating the initiation of the expression of the MOR gene in lymphocytes. The electrophoretic mobility shift assay showed that two transcription factors, Sp1 and YY1, were able to bind the promoter region. Using sequence overlapping probes and mutation assays, we determined that the CCC sequence of Sp1 and the GGC sequence of YY1 binding elements were core sequences, and replacement of these sequences lead to substantial loss of promoter activity. Stimulation with morphine was capable of up-regulating the intracellular level of Sp1 and YY1 proteins. Chromatin immunoprecipitation assays showed that the blockage of naloxone is achieved through down-regulation of transcription factor YY1. Furthermore, coimmunoprecipitation and transfection assays confirmed that the functional interaction of Sp1 and YY1 transcription factors was a crucial step in the initiation of expression of the MOR in lymphocytes. Thus, we conclude that the cooperative interaction of Sp1 and YY1 transcription factors is the critical event triggering the initiation of transcription of the MOR gene in lymphocytes, and this finding will be helpful to understand the pharmacological effect of morphine on lymphocytes.

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supporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes

Liu

Wang

et al. 2007

J of Cellular Biochemistry

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“…During the early part of this century, there was considerable interest in the biological role of methylation and the regulation of genes such as RELN, DRD2, OPRM, HTR2A, COMT, ALOX5, and others that are downregulated in psychosis Andria and Simon, 1999;Chen et al, 2002;Zhang et al, 2004;Abdolmaleky et al, 2005Abdolmaleky et al, , 2006Polesskaya et al, 2006). Methylation was proposed as a mechanism for the silencing of genes expressed in cortical neurons in SZ.…”

Section: Dna Methylation In Sz and Bp+mentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

242

214

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Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+ ) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+ .

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“…This leads to the recruitment of repressor proteins that facilitate the deacetylation of the relevant histones. It has already been established that neuronal cells that do not express the OPRM1 promoter are methylated, while OPRM1 -expressing neuronal cells are not, confirming the importance of DNA methylation in the activation of this gene (Andria ML, 1999). In addition, former heroin addicts have been found to display hypermethylation of the OPRM1 promoter in the peripheral lymphocytes, regardless of whether or not they were HIV-infected, illustrating the epigenetic ramifications of long-term use (Nielsen DA, 2009).…”

Section: Epigenetics Of Drug Abuse and Its Impact On Hiv-1 Infectionmentioning

confidence: 81%

Epigenetics, Drugs of Abuse, and the Retroviral Promoter

Shirazi

Shah

Sagar

et al. 2013

J Neuroimmune Pharmacol

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Drug abuse alone has been shown to cause epigenetic changes in brain tissue that have been shown to play roles in addictive behaviors. In conjunction with HIV-1 infection, it can cause epigenetic changes at the viral promoter that can result in altered gene expression, and exacerbate disease progression overall. This review entails an in-depth look at research conducted on the epigenetic effects of three of the most widely abused drugs (cannabinoids, opioids, and cocaine), with a particular focus on the mechanisms through which these drugs interact with HIV-1 infection at the viral promoter. Here we discuss the impact of this interplay on disease progression from the point of view of the nature of gene regulation at the level of chromatin accessibility, chromatin remodeling, and nucleosome repositioning. Given the importance of chromatin remodeling and DNA methylation in controlling the retroviral promoter, and the high susceptibility of the drug abusing population of individuals to HIV infection, it would be beneficial to understand the way in which the host genome is modified and regulated by drugs of abuse.

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Localization of promoter elements in the human mu-opioid receptor gene and regulation by DNA methylation

Cited by 35 publications

References 65 publications

The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes

The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Epigenetics, Drugs of Abuse, and the Retroviral Promoter

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