Limits...
Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen-activated protein kinase network: a cross-sectional study.

Carmona JJ, Sofer T, Hutchinson J, Cantone L, Coull B, Maity A, Vokonas P, Lin X, Schwartz J, Baccarelli AA - Environ Health (2014)

Bottom Line: DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks.Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes.No associations were found with the NF-κB pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Human Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. abaccare@hsph.harvard.edu.

ABSTRACT

Background: Exposure to air particulate matter is known to elevate blood biomarkers of inflammation and to increase cardiopulmonary morbidity and mortality. Major components of airborne particulate matter typically include black carbon from traffic and sulfates from coal-burning power plants. DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks. The underlying mechanisms may include epigenetic modulation of major inflammatory pathways, yet the details remain unclear.

Methods: We sought to elucidate how short-term exposure to air pollution components, singly and/or in combination, alter blood DNA methylation in certain inflammation-associated gene networks, MAPK and NF-κB, which may transmit the environmental signal(s) and influence the inflammatory pathway in vivo. To this end, we utilized a custom-integrated workflow-molecular processing, pollution surveillance, biostatical analysis, and bioinformatic visualization-to map novel human (epi)gene pathway-environment interactions.

Results: Specifically, out of 84 MAPK pathway genes considered, we identified 11 whose DNA methylation status was highly associated with black carbon exposure, after adjusting for potential confounders-age, sulfate exposure, smoking, blood cell composition, and blood pressure. Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes. No associations were found with the NF-κB pathway.

Conclusion: Exposure to short-term air pollution components thus resulted in quantifiable epigenetic changes in the promoter areas of MAPK pathway genes. Bioinformatic mapping of single- vs. multi-exposure-associated epigenetic changes suggests that these alterations might affect biological pathways in nuanced ways that are not simply additive or fully predictable via individual-level exposure assessments.

Show MeSH

Related in: MedlinePlus

Methylation coefficients of our (epi)gene hits within the broader MAPK signaling system. A nexus integrating all BioCarta MAP kinase genes to other previously studied MAPK networks is diagramed, wherein nodes representing the genes within the BioCarta MAP kinase pathway (84 total) are outlined and labeled in dark black. Arrows indicate known direction of action. Methylation coefficients (from Table 3) are represented here in a scale from blue (negative values), to white (zero), to orange (positive values). For simplicity, both unmeasured values and zero are represented in white. Exposure-specific MAPK coefficients are shown across all three of our models: (a) black carbon; (b) sulfates; and (c) the multi-pollutant paradigm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4273424&req=5

Fig2: Methylation coefficients of our (epi)gene hits within the broader MAPK signaling system. A nexus integrating all BioCarta MAP kinase genes to other previously studied MAPK networks is diagramed, wherein nodes representing the genes within the BioCarta MAP kinase pathway (84 total) are outlined and labeled in dark black. Arrows indicate known direction of action. Methylation coefficients (from Table 3) are represented here in a scale from blue (negative values), to white (zero), to orange (positive values). For simplicity, both unmeasured values and zero are represented in white. Exposure-specific MAPK coefficients are shown across all three of our models: (a) black carbon; (b) sulfates; and (c) the multi-pollutant paradigm.

Mentions: In the present work, however, our 27 (epi)gene hits in the MAPK pathway do not share any obvious physiological link, collectively, within some unified cardiopulmonary pathway relevant to air pollution—thus perhaps constituting a novel epigenetic/signaling “crossroads” of exposure-associated genes relevant to the processing of environmental PM signals in vivo. To help visualize this dynamic system, we next used an integrated bioinformatic approach to overlay our DNA methylation coefficients (from Table 3) onto an expanded MAPK signaling map. In Figure 2, we can best appreciate the following points: (i.) our initial set of 84 MAPK genes (dark circles) map widely across the broadened MAPK signaling system, thereby ensuring that most branches of the network were aptly queried via our stepwise-CAA method; (ii.) the distribution of exposure-specific MAPK hits across the multi-pollution model (Figure 2c) is not simply an aggregate of signaling components found in the two other models, BC (2a) and sulfates (2b).Figure 2


Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen-activated protein kinase network: a cross-sectional study.

Carmona JJ, Sofer T, Hutchinson J, Cantone L, Coull B, Maity A, Vokonas P, Lin X, Schwartz J, Baccarelli AA - Environ Health (2014)

Methylation coefficients of our (epi)gene hits within the broader MAPK signaling system. A nexus integrating all BioCarta MAP kinase genes to other previously studied MAPK networks is diagramed, wherein nodes representing the genes within the BioCarta MAP kinase pathway (84 total) are outlined and labeled in dark black. Arrows indicate known direction of action. Methylation coefficients (from Table 3) are represented here in a scale from blue (negative values), to white (zero), to orange (positive values). For simplicity, both unmeasured values and zero are represented in white. Exposure-specific MAPK coefficients are shown across all three of our models: (a) black carbon; (b) sulfates; and (c) the multi-pollutant paradigm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4273424&req=5

Fig2: Methylation coefficients of our (epi)gene hits within the broader MAPK signaling system. A nexus integrating all BioCarta MAP kinase genes to other previously studied MAPK networks is diagramed, wherein nodes representing the genes within the BioCarta MAP kinase pathway (84 total) are outlined and labeled in dark black. Arrows indicate known direction of action. Methylation coefficients (from Table 3) are represented here in a scale from blue (negative values), to white (zero), to orange (positive values). For simplicity, both unmeasured values and zero are represented in white. Exposure-specific MAPK coefficients are shown across all three of our models: (a) black carbon; (b) sulfates; and (c) the multi-pollutant paradigm.
Mentions: In the present work, however, our 27 (epi)gene hits in the MAPK pathway do not share any obvious physiological link, collectively, within some unified cardiopulmonary pathway relevant to air pollution—thus perhaps constituting a novel epigenetic/signaling “crossroads” of exposure-associated genes relevant to the processing of environmental PM signals in vivo. To help visualize this dynamic system, we next used an integrated bioinformatic approach to overlay our DNA methylation coefficients (from Table 3) onto an expanded MAPK signaling map. In Figure 2, we can best appreciate the following points: (i.) our initial set of 84 MAPK genes (dark circles) map widely across the broadened MAPK signaling system, thereby ensuring that most branches of the network were aptly queried via our stepwise-CAA method; (ii.) the distribution of exposure-specific MAPK hits across the multi-pollution model (Figure 2c) is not simply an aggregate of signaling components found in the two other models, BC (2a) and sulfates (2b).Figure 2

Bottom Line: DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks.Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes.No associations were found with the NF-κB pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Human Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. abaccare@hsph.harvard.edu.

ABSTRACT

Background: Exposure to air particulate matter is known to elevate blood biomarkers of inflammation and to increase cardiopulmonary morbidity and mortality. Major components of airborne particulate matter typically include black carbon from traffic and sulfates from coal-burning power plants. DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks. The underlying mechanisms may include epigenetic modulation of major inflammatory pathways, yet the details remain unclear.

Methods: We sought to elucidate how short-term exposure to air pollution components, singly and/or in combination, alter blood DNA methylation in certain inflammation-associated gene networks, MAPK and NF-κB, which may transmit the environmental signal(s) and influence the inflammatory pathway in vivo. To this end, we utilized a custom-integrated workflow-molecular processing, pollution surveillance, biostatical analysis, and bioinformatic visualization-to map novel human (epi)gene pathway-environment interactions.

Results: Specifically, out of 84 MAPK pathway genes considered, we identified 11 whose DNA methylation status was highly associated with black carbon exposure, after adjusting for potential confounders-age, sulfate exposure, smoking, blood cell composition, and blood pressure. Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes. No associations were found with the NF-κB pathway.

Conclusion: Exposure to short-term air pollution components thus resulted in quantifiable epigenetic changes in the promoter areas of MAPK pathway genes. Bioinformatic mapping of single- vs. multi-exposure-associated epigenetic changes suggests that these alterations might affect biological pathways in nuanced ways that are not simply additive or fully predictable via individual-level exposure assessments.

Show MeSH
Related in: MedlinePlus