Rich-recent methylation article

Discussion in 'Fibromyalgia Main Forum' started by ulala, Oct 18, 2010.

  1. ulala

    ulala New Member

    Have you seeen this?
  2. richvank

    richvank New Member

    Hi, ulala.

    Thanks for posting this, but I was not able to get this link to work. Is it correct?

  3. ulala

    ulala New Member

    Neuromol Med : DOI 10.1007/s12017-010-8138-2

    Functional Genomics of Serotonin Receptor 2A (HTR2A): Interaction of Polymorphism, Methylation, Expression and Disease Association

    Virginia R. Falkenberg • Brian M. Gurbaxani • Elizabeth R. Unger • Mangalathu S. Rajeevan
    Division of Viral and Rickettsial Diseases, Centers for Disease Control & Prevention, Atlanta, GA 30333, USA

    Published online: 13 October 2010

    (c) The Author(s) 2010. This article is published with open access at

    This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.



    Serotonergic neurotransmission plays a key role in the pathophysiology of neuropsychiatric illnesses. The functional significance of a promoter polymorphism, ?1438G/A (rs6311), in one of the major genes of this system (serotonin receptor 2A, HTR2A) remains poorly understood in the context of epigenetic factors, transcription factors and endocrine influences.

    We used functional and structural equation modeling (SEM) approaches to assess the contributions of the polymorphism (rs6311), DNA methylation and clinical variables to HTR2A expression in chronic fatigue syndrome (CFS) subjects from a population-based study.

    HTR2A was up-regulated in CFS through allele-specific expression modulated by transcription factors at critical sites in its promoter: an E47 binding site at position ?1,438, (created by the A-allele of rs6311 polymorphism), a glucocorticoid receptor (GR) binding site encompassing a CpG at position ?1,420, and Sp1 binding at CpG methylation site ?1,224.

    Methylation at ?1,420 was strongly correlated with methylation at ?1,439, a CpG site that is dependent upon the G-allele of rs6311 at position ?1,438. SEM revealed a strong negative interaction between E47 and GR binding (in conjunction with cortisol level) on HTR2A expression. This study suggests that the promoter polymorphism (rs6311) can affect both transcription factor binding and promoter methylation, and this along with an individual’s stress response can impact the rate of HTR2A transcription in a genotype and methylation-dependent manner.

    This study can serve as an example for deciphering the molecular determinants of transcriptional regulation of major genes of medical importance by integrating functional genomics and SEM approaches.

    Confirmation in an independent study population is required.

    Full Text article at :

  4. richvank

    richvank New Member

  5. ulala

    ulala New Member

    I'll have to re-read it to try to make some sense of it.

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