			Home About us Contact

Methylation Marks (methylation + mark)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Environmental epigenomics in human health and disease

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2008
Dana C. Dolinoy
Abstract The epigenome consists of the DNA methylation marks and histone modifications involved in controlling gene expression. It is accurately reproduced during mitosis and can be inherited transgenerationally. The innate plasticity of the epigenome also enables it to be reprogrammed by nutritional, chemical, and physical factors. Imprinted genes and metastable epialleles represent two classes of genes that are particularly susceptible to environmental factors because their regulation is tightly linked to epigenetic mechanisms. To fully understand the etiology of the most devastating diseases that plague humans, the full complexity of the human epigenome will ultimately need to be characterized. Moreover, the elucidation of the interaction of the environment with the epigenome should allow for the development of novel epigenetic-based diagnostic, prevention, and therapeutic strategies for human diseases. Herein, we introduce the emerging field of environmental epigenomics, discuss the importance of imprinted genes and metastable epialleles as epigenetically labile genomic targets, and endorse the genome-wide identification of the full suite of epigenetically labile targets in both the mouse and human genomes. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source]

Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010
William F. Carson
Abstract Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4+ T-cell responses remains unclear. In the present study, CD4+ T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro. CD4+CD62L+ T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4+CD62L+ T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the TH1 or TH2 lineage. Repressive histone methylation marks were also evident at promoter regions for the TH1 cytokine IFN-, and the TH2 transcription factor GATA-3 in naïve CD4+ T cells from CLP mice. These results provide evidence that CD4+ T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription. [source]

Unravelling a histone code for malaria virulence

MOLECULAR MICROBIOLOGY, Issue 6 2007
Christy A. Comeaux
Summary Epigenetic phenomena have been shown to play a role in the regulated expression of virulence genes in several pathogenic organisms, including the var gene family in Plasmodium falciparum. A better understanding of how P. falciparum can both maintain a single active var gene locus through many erythrocytic cycles and also achieve successive switching to different loci in order to evade the host immune system is greatly needed. Disruption of this tightly co-ordinated expression system presents an opportunity for increased clearance of the parasites by the immune system and, in turn, reduced mortality and morbidity. In the current issue of Molecular Microbiology, Lopez-Rubio and colleagues investigate the correlation of specific post-translational histone modifications with different transcriptional states of a single var gene, var2csa. Quantitative chromatin immunoprecipitation is used to demonstrate that different histone methylation marks are enriched at the 5, flanking and coding regions of active, poised or silenced var genes. They identify an increase of H3K4me2 and H3K4me3 in the 5, flanking region of an active var locus and expand on an earlier finding that H3K9me3 is enriched in the coding regions of silenced var genes. The authors also present evidence that H3K4me2 bookmarks the active var gene locus during later developmental stages for expression in the subsequent asexual cycle, hinting at a potential mechanism for transcriptional ,memory'. The stage is now set for work generating a complete catalogue of all histone modifications associated with var gene regulation as well as functional studies striving to uncover the precise mechanisms underlying these observations. [source]

Overexpression of the growth arrest and DNA damage,induced 45, gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells

ARTHRITIS & RHEUMATISM, Issue 5 2010
Yaping Li
Objective Demethylation of CD11a and CD70 regulatory regions in CD4+ T cells contributes to the development of autoreactivity and overstimulation of autoantibodies. Because growth arrest and DNA damage,induced 45, (GADD45,) reduces epigenetic silencing of genes by removing methylation marks, this study examined whether the gadd45A gene could contribute to autoimmunity by promoting DNA demethylation in T cells from patients with systemic lupus erythematosus (SLE). Methods Levels of GADD45,, CD11a, and CD70 messenger RNA (mRNA) and protein were detected by real-time reverse transcription,polymerase chain reaction and Western blotting or flow cytometry. Global DNA methylation was evaluated using Methylamp global DNA methylation quantification kits. Detection of CD4+ T cell proliferation and autologous B cell IgG antibodies was performed using commercially available kits. CD11a and CD70 promoter methylation was determined with bisulfite sequencing. Results Elevated gadd45A mRNA expression and global DNA hypomethylation were observed in CD4+ T cells from SLE patients. The levels of gadd45A mRNA were inversely proportional to the levels of DNA methylation. Positive correlations were found between gadd45A and CD11a/CD70 mRNA levels. Expression of gadd45A mRNA was increased in CD4+ T cells following ultraviolet B irradiation, and this was accompanied by increased levels of CD11a and CD70 mRNA. Moreover, increased expression of gadd45A, CD11a, and CD70 mRNA was accompanied by increased autoreactivity and excessive B cell stimulation in gadd45A -transfected CD4+ T cells. CD11a promoter methylation was also significantly reduced in transfected cells. Transfection of gadd45A small interfering RNA inhibited the autoreactivity of SLE CD4+ T cells and led to significant increases in the methylation levels of the CD11a and CD70 promoter regions. Conclusion These findings indicate that gadd45A may contribute to lupus-like autoimmunity by promoting DNA demethylation in SLE CD4+ T cells. [source]