Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts

Although selection of the early age at puberty in gilts will make for a favorable effect on the reproductivity of sow, a large proportion of phenotypic variation in age at puberty of gilts cannot be explained by genetics. Previous studies have implicated hypothalamic DNA methylation in the onset of...

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Main Authors: Xiaolong Yuan, Xiaofeng Zhou, Zitao Chen, Yingting He, Yaru Kong, Shaopan Ye, Ning Gao, Zhe Zhang, Hao Zhang, Jiaqi Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2019.00228/full
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author Xiaolong Yuan
Xiaofeng Zhou
Zitao Chen
Yingting He
Yaru Kong
Shaopan Ye
Ning Gao
Zhe Zhang
Hao Zhang
Jiaqi Li
author_facet Xiaolong Yuan
Xiaofeng Zhou
Zitao Chen
Yingting He
Yaru Kong
Shaopan Ye
Ning Gao
Zhe Zhang
Hao Zhang
Jiaqi Li
author_sort Xiaolong Yuan
collection DOAJ
description Although selection of the early age at puberty in gilts will make for a favorable effect on the reproductivity of sow, a large proportion of phenotypic variation in age at puberty of gilts cannot be explained by genetics. Previous studies have implicated hypothalamic DNA methylation in the onset of puberty in mammals. However, the underlying molecular mechanism regarding the regulation of the onset of puberty has remained largely unexplored in gilts. Herein, the genome-scale DNA methylation of hypothalamus was acquired, using the reduced representation bisulfite sequencing, to compare and describe the changes of DNA methylation across Pre-, In- and Post-pubertal gilts. In this study, the average methylation levels of CpGs and CpHs (where H = C, T, or A) in CpG islands- and gene-related regions were gradually decreased in hypothalamic methylomes during the pubertal transition. Comparisons of Pre- vs. In-, In- vs. Post-, and Pre- vs. Post-pubertal stage revealed that there were 85726, 92914, and 100421 differentially methylated CpGs and 5940, 14804, and 16893 differentially methylated CpHs (where H = C, T, or A) in the hypothalamic methylomes. The methylation changes of CpHs were more dynamic than that of CpGs, and methylation changes of CpGs and CpHs were likely to be, respectively, involved in the developmental processes of reproduction and the molecular processes of cellular communications in the hypothalamus. Moreover, methylation changes of CpHs were observed to overrepresent in the quantitative trait loci of age at puberty, and the biological function of these CpH methylation changes was enriched in the pancreas development in gilts. Furthermore, the mRNA levels of several differentially CpG or CpH methylated genes related to the transcription of RNA II polymerase, GnRH signaling pathway, Estrogen signaling pathway, PI3K-AKt signaling pathway, and Insulin signaling pathway, including MAX, MMP2, FGF11, IGF1R, FGF21, and GSK3B, were significantly changed across these pubertal stages in the hypothalamus. These results will help our understanding of how DNA methylation contributes to phenotypic variation of age at puberty.
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spelling doaj.art-f9e4677efef847d383c2d9c2d4736cb42022-12-21T18:22:16ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-03-011010.3389/fgene.2019.00228440819Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in GiltsXiaolong Yuan0Xiaofeng Zhou1Zitao Chen2Yingting He3Yaru Kong4Shaopan Ye5Ning Gao6Zhe Zhang7Hao Zhang8Jiaqi Li9Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Guangzhou Higher Education Mega Center, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaAlthough selection of the early age at puberty in gilts will make for a favorable effect on the reproductivity of sow, a large proportion of phenotypic variation in age at puberty of gilts cannot be explained by genetics. Previous studies have implicated hypothalamic DNA methylation in the onset of puberty in mammals. However, the underlying molecular mechanism regarding the regulation of the onset of puberty has remained largely unexplored in gilts. Herein, the genome-scale DNA methylation of hypothalamus was acquired, using the reduced representation bisulfite sequencing, to compare and describe the changes of DNA methylation across Pre-, In- and Post-pubertal gilts. In this study, the average methylation levels of CpGs and CpHs (where H = C, T, or A) in CpG islands- and gene-related regions were gradually decreased in hypothalamic methylomes during the pubertal transition. Comparisons of Pre- vs. In-, In- vs. Post-, and Pre- vs. Post-pubertal stage revealed that there were 85726, 92914, and 100421 differentially methylated CpGs and 5940, 14804, and 16893 differentially methylated CpHs (where H = C, T, or A) in the hypothalamic methylomes. The methylation changes of CpHs were more dynamic than that of CpGs, and methylation changes of CpGs and CpHs were likely to be, respectively, involved in the developmental processes of reproduction and the molecular processes of cellular communications in the hypothalamus. Moreover, methylation changes of CpHs were observed to overrepresent in the quantitative trait loci of age at puberty, and the biological function of these CpH methylation changes was enriched in the pancreas development in gilts. Furthermore, the mRNA levels of several differentially CpG or CpH methylated genes related to the transcription of RNA II polymerase, GnRH signaling pathway, Estrogen signaling pathway, PI3K-AKt signaling pathway, and Insulin signaling pathway, including MAX, MMP2, FGF11, IGF1R, FGF21, and GSK3B, were significantly changed across these pubertal stages in the hypothalamus. These results will help our understanding of how DNA methylation contributes to phenotypic variation of age at puberty.https://www.frontiersin.org/article/10.3389/fgene.2019.00228/fullgenome-wide DNA methylationhypothalamusQTL of age at puberty in pigsonset of pubertygilts
spellingShingle Xiaolong Yuan
Xiaofeng Zhou
Zitao Chen
Yingting He
Yaru Kong
Shaopan Ye
Ning Gao
Zhe Zhang
Hao Zhang
Jiaqi Li
Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
Frontiers in Genetics
genome-wide DNA methylation
hypothalamus
QTL of age at puberty in pigs
onset of puberty
gilts
title Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
title_full Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
title_fullStr Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
title_full_unstemmed Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
title_short Genome-Wide DNA Methylation Analysis of Hypothalamus During the Onset of Puberty in Gilts
title_sort genome wide dna methylation analysis of hypothalamus during the onset of puberty in gilts
topic genome-wide DNA methylation
hypothalamus
QTL of age at puberty in pigs
onset of puberty
gilts
url https://www.frontiersin.org/article/10.3389/fgene.2019.00228/full
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