Genome-wide DNA methylome variation in two genetically distinct chicken lines using MethylC-seq.
BACKGROUND
DNA cytosine methylation is an important epigenetic modification that has significant effects on a variety of biological processes in animals. Avian species hold a crucial position in evolutionary history. In this study, we used whole-genome bisulfite sequencing (MethylC-seq) to generate single base methylation profiles of lungs in two genetically distinct and highly inbred chicken lines (Fayoumi and Leghorn) that differ in genetic resistance to multiple pathogens, and we explored the potential regulatory role of DNA methylation associated with immune response differences between the two chicken lines.


METHODS
The MethylC-seq was used to generate single base DNA methylation profiles of Fayoumi and Leghorn birds. In addition, transcriptome profiling using RNA-seq from the same chickens and tissues were obtained to interrogate how DNA methylation regulates gene transcription on a genome-wide scale.


RESULTS
The general DNA methylation pattern across different regions of genes was conserved compared to other species except for hyper-methylation of repeat elements, which was not observed in chicken. The methylation level of miRNA and pseudogene promoters was high, which indicates that silencing of these genes may be partially due to promoter hyper-methylation. Interestingly, the promoter regions of more recently evolved genes tended to be more highly methylated, whereas the gene body regions of evolutionarily conserved genes were more highly methylated than those of more recently evolved genes. Immune-related GO (Gene Ontology) terms were significantly enriched from genes within the differentially methylated regions (DMR) between Fayoumi and Leghorn, which implicates DNA methylation as one of the regulatory mechanisms modulating immune response differences between these lines.


CONCLUSIONS
This study establishes a single-base resolution DNA methylation profile of chicken lung and suggests a regulatory role of DNA methylation in controlling gene expression and maintaining genome transcription stability. Furthermore, profiling the DNA methylomes of two genetic lines that differ in disease resistance provides a unique opportunity to investigate the potential role of DNA methylation in host disease resistance. Our study provides a foundation for future studies on epigenetic modulation of host immune response to pathogens in chickens.
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.|CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
Jinxiu
J
Li
Core Genomic Facility, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
Rujiao
R
Li
Department of Animal Science, University of California, Davis, CA, 95616, USA.
Ying
Y
Wang
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.
Xiaoxiang
X
Hu
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.
Yiqiang
Y
Zhao
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.
Li
L
Li
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.
Chungang
C
Feng
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China.
Xiaorong
X
Gu
Core Genomic Facility, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
Fang
F
Liang
Department of Animal Science, Iowa State University, Ames, IA, 50011, USA.
Susan J
SJ
Lamont
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
Songnian
S
Hu
Department of Animal Science, University of California, Davis, CA, 95616, USA. hzhou@ucdavis.edu.|Department of Poultry Science, Texas A&M University, College Station, TX, 77845, USA. hzhou@ucdavis.edu.
Huaijun
H
Zhou
The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing, 100193, China. ninglcau@cau.edu.cn.|National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, China. ninglcau@cau.edu.cn.|College of Animal Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China. ninglcau@cau.edu.cn.
Ning
N
Li
D000818:Animals; D001482:Base Composition; D002645:Chickens / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D055106:Genome-Wide Association Study / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D008168:Lung / Q000378:metabolism; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D011544:Pseudogenes; D012091:Repetitive Sequences, Nucleic Acid; D059467:Transcriptome