Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process
Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore...
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| Published in | Frontiers in genetics Vol. 11; p. 626536 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
14.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1664-8021 1664-8021 |
| DOI | 10.3389/fgene.2020.626536 |
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| Abstract | Background:
Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process.
Methods:
Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation.
Results:
A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty.
Conclusion:
Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process. |
|---|---|
| AbstractList | Background:
Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process.
Methods:
Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation.
Results:
A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty.
Conclusion:
Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process. Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process. Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation. A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty. Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process. Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process.Methods: Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation.Results: A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty.Conclusion: Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process. Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process. Methods: Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation. Results: A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty. Conclusion: Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process.Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process. Methods: Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation. Results: A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty. Conclusion: Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process. |
| Author | Zhou, Shasha Shen, Yihang Li, Hua Zhao, Xiaodong Sun, Jielin |
| AuthorAffiliation | 1 Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory for Systems Biomedicine, Shanghai Jiao Tong University , Shanghai , China 2 Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University , Shanghai , China 3 Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai , China |
| AuthorAffiliation_xml | – name: 2 Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University , Shanghai , China – name: 3 Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai , China – name: 1 Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory for Systems Biomedicine, Shanghai Jiao Tong University , Shanghai , China |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33381157$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2020 Shen, Zhou, Zhao, Li and Sun. Copyright © 2020 Shen, Zhou, Zhao, Li and Sun. 2020 Shen, Zhou, Zhao, Li and Sun |
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| Keywords | DNA methylation DNA hydroxymethylation ARC puberty onset GnRH |
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| License | Copyright © 2020 Shen, Zhou, Zhao, Li and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Computational Genomics, a section of the journal Frontiers in Genetics Edited by: Yuriy L. Orlov, I.M. Sechenov First Moscow State Medical University, Russia Reviewed by: Julia Fedotova, Russian Academy of Sciences, Russia; Jun Wu, East China Normal University, China; Wen-Lian Chen, Shanghai University of Traditional Chinese Medicine, China These authors have contributed equally to this work |
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Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The... Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic... Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The... |
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| Title | Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process |
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