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Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature.

Liu C, Xu J, Chen Y, Guo X, Zheng Y, Wang Q, Chen Y, Ni Y, Zhu Y, Joyce BT, Baccarelli A, Deng F, Zhang W, Hou L - Environ Health (2015)

Bottom Line: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5.Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses.Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA. cliu55@uic.edu.

ABSTRACT

Background: Current studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions.

Methods: In this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 μm).

Results: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses.

Conclusions: Our study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.

No MeSH data available.


Related in: MedlinePlus

Enriched functional annotations among differential H3K27ac loci. Proximal gene enrichments for differential H3K27ac loci were analyzed using a GO biological processes; and b PANTHER pathways. Circle size is proportional to the number of identified genes. Circle transparency is proportional to fold enrichment relative to the human genome. Functional annotations were ordered by FDR derived from hypergeometric test. Red vertical lines indicate the cutoff at 5 % FDR. GO: gene ontology; FDR: false discovery rate
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Fig3: Enriched functional annotations among differential H3K27ac loci. Proximal gene enrichments for differential H3K27ac loci were analyzed using a GO biological processes; and b PANTHER pathways. Circle size is proportional to the number of identified genes. Circle transparency is proportional to fold enrichment relative to the human genome. Functional annotations were ordered by FDR derived from hypergeometric test. Red vertical lines indicate the cutoff at 5 % FDR. GO: gene ontology; FDR: false discovery rate

Mentions: Gene set enrichment analysis was performed to evaluate the genes annotated by the identified differential H3K27ac loci using the GREAT tools. Additional file 4: Table S4 shows significantly enriched GO biological processes and PANTHER pathways. We found that most of the associated genes were involved in the activation of cellular responses to wounding and stimulus, suggesting an enhancer-mediated cell activation mechanism in response to higher PM2.5 exposure. We also found differential H3K27ac loci were most significantly enriched in pathways related to immune response, including T-cell and B-cell activation (Fig. 3). Interestingly, we found that a pathway related to Alzheimer’s disease was enriched in our results.Fig. 3


Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature.

Liu C, Xu J, Chen Y, Guo X, Zheng Y, Wang Q, Chen Y, Ni Y, Zhu Y, Joyce BT, Baccarelli A, Deng F, Zhang W, Hou L - Environ Health (2015)

Enriched functional annotations among differential H3K27ac loci. Proximal gene enrichments for differential H3K27ac loci were analyzed using a GO biological processes; and b PANTHER pathways. Circle size is proportional to the number of identified genes. Circle transparency is proportional to fold enrichment relative to the human genome. Functional annotations were ordered by FDR derived from hypergeometric test. Red vertical lines indicate the cutoff at 5 % FDR. GO: gene ontology; FDR: false discovery rate
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537530&req=5

Fig3: Enriched functional annotations among differential H3K27ac loci. Proximal gene enrichments for differential H3K27ac loci were analyzed using a GO biological processes; and b PANTHER pathways. Circle size is proportional to the number of identified genes. Circle transparency is proportional to fold enrichment relative to the human genome. Functional annotations were ordered by FDR derived from hypergeometric test. Red vertical lines indicate the cutoff at 5 % FDR. GO: gene ontology; FDR: false discovery rate
Mentions: Gene set enrichment analysis was performed to evaluate the genes annotated by the identified differential H3K27ac loci using the GREAT tools. Additional file 4: Table S4 shows significantly enriched GO biological processes and PANTHER pathways. We found that most of the associated genes were involved in the activation of cellular responses to wounding and stimulus, suggesting an enhancer-mediated cell activation mechanism in response to higher PM2.5 exposure. We also found differential H3K27ac loci were most significantly enriched in pathways related to immune response, including T-cell and B-cell activation (Fig. 3). Interestingly, we found that a pathway related to Alzheimer’s disease was enriched in our results.Fig. 3

Bottom Line: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5.Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses.Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA. cliu55@uic.edu.

ABSTRACT

Background: Current studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions.

Methods: In this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 μm).

Results: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses.

Conclusions: Our study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.

No MeSH data available.


Related in: MedlinePlus