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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

Global profiles of H3K27ac overlapped with promoters and enhancers. Global H3K27ac signal densities normalized by input were determined in a 20 kb-window surrounding a the center of ENCODE-detected enhancers; and b the TSS of human RefSeq genes. The red curve represents the average H3K27ac signal density in the high-exposed group and the blue curve represents the average density in the low-exposed group. Both promoters and enhancers show global elevated H3K27ac modification levels in the individuals exposed to higher PM2.5 (red). TSS: transcription start site
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Fig2: Global profiles of H3K27ac overlapped with promoters and enhancers. Global H3K27ac signal densities normalized by input were determined in a 20 kb-window surrounding a the center of ENCODE-detected enhancers; and b the TSS of human RefSeq genes. The red curve represents the average H3K27ac signal density in the high-exposed group and the blue curve represents the average density in the low-exposed group. Both promoters and enhancers show global elevated H3K27ac modification levels in the individuals exposed to higher PM2.5 (red). TSS: transcription start site

Mentions: For each individual, both ChIP and input samples were sequenced. After conventional quality control, around 2–9 million unique reads were mapped to the reference genome (hg19) in the ChIP samples, in contrast to the 4–12 million reads in the input samples (Additional file 1: Table S1). In total, 7000 ~ 54000 peaks were called using a stringent peak detection threshold p-value of p < 10−5 (Additional file 2: Table S2). Among differentially modified H3K27ac loci, 1080 loci were induced in the group with high PM2.5 exposure, and 158 loci were suppressed (Additional file 3: Table S3). In general, individuals with higher PM2.5 tended to have a higher number of peaks. In addition, a similar global pattern was observed from aggregation plots of H3K27ac on promoter and enhancer regions (Fig. 2). H3K27ac peaks were clearly overlapped in promoter and enhancer regions, consistent with the putative role of H3K27ac as a promoter and enhancer marker. Both the TSS and enhancer peaks were higher in the individuals with high PM2.5 exposure compared to low-exposed individuals. These findings could indicate global enhancement of gene expression due to the exposure to PM2.5 pollutants.Fig. 2


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)

Global profiles of H3K27ac overlapped with promoters and enhancers. Global H3K27ac signal densities normalized by input were determined in a 20 kb-window surrounding a the center of ENCODE-detected enhancers; and b the TSS of human RefSeq genes. The red curve represents the average H3K27ac signal density in the high-exposed group and the blue curve represents the average density in the low-exposed group. Both promoters and enhancers show global elevated H3K27ac modification levels in the individuals exposed to higher PM2.5 (red). TSS: transcription start site
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Global profiles of H3K27ac overlapped with promoters and enhancers. Global H3K27ac signal densities normalized by input were determined in a 20 kb-window surrounding a the center of ENCODE-detected enhancers; and b the TSS of human RefSeq genes. The red curve represents the average H3K27ac signal density in the high-exposed group and the blue curve represents the average density in the low-exposed group. Both promoters and enhancers show global elevated H3K27ac modification levels in the individuals exposed to higher PM2.5 (red). TSS: transcription start site
Mentions: For each individual, both ChIP and input samples were sequenced. After conventional quality control, around 2–9 million unique reads were mapped to the reference genome (hg19) in the ChIP samples, in contrast to the 4–12 million reads in the input samples (Additional file 1: Table S1). In total, 7000 ~ 54000 peaks were called using a stringent peak detection threshold p-value of p < 10−5 (Additional file 2: Table S2). Among differentially modified H3K27ac loci, 1080 loci were induced in the group with high PM2.5 exposure, and 158 loci were suppressed (Additional file 3: Table S3). In general, individuals with higher PM2.5 tended to have a higher number of peaks. In addition, a similar global pattern was observed from aggregation plots of H3K27ac on promoter and enhancer regions (Fig. 2). H3K27ac peaks were clearly overlapped in promoter and enhancer regions, consistent with the putative role of H3K27ac as a promoter and enhancer marker. Both the TSS and enhancer peaks were higher in the individuals with high PM2.5 exposure compared to low-exposed individuals. These findings could indicate global enhancement of gene expression due to the exposure to PM2.5 pollutants.Fig. 2

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