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Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood
Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only expla...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923870/ https://www.ncbi.nlm.nih.gov/pubmed/27349168 http://dx.doi.org/10.1038/srep28657 |
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author | Almstrup, Kristian Lindhardt Johansen, Marie Busch, Alexander S. Hagen, Casper P. Nielsen, John E. Petersen, Jørgen Holm Juul, Anders |
author_facet | Almstrup, Kristian Lindhardt Johansen, Marie Busch, Alexander S. Hagen, Casper P. Nielsen, John E. Petersen, Jørgen Holm Juul, Anders |
author_sort | Almstrup, Kristian |
collection | PubMed |
description | Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing. |
format | Online Article Text |
id | pubmed-4923870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49238702016-06-28 Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood Almstrup, Kristian Lindhardt Johansen, Marie Busch, Alexander S. Hagen, Casper P. Nielsen, John E. Petersen, Jørgen Holm Juul, Anders Sci Rep Article Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing. Nature Publishing Group 2016-06-28 /pmc/articles/PMC4923870/ /pubmed/27349168 http://dx.doi.org/10.1038/srep28657 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Almstrup, Kristian Lindhardt Johansen, Marie Busch, Alexander S. Hagen, Casper P. Nielsen, John E. Petersen, Jørgen Holm Juul, Anders Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title | Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title_full | Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title_fullStr | Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title_full_unstemmed | Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title_short | Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood |
title_sort | pubertal development in healthy children is mirrored by dna methylation patterns in peripheral blood |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923870/ https://www.ncbi.nlm.nih.gov/pubmed/27349168 http://dx.doi.org/10.1038/srep28657 |
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