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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...

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Autores principales: Almstrup, Kristian, Lindhardt Johansen, Marie, Busch, Alexander S., Hagen, Casper P., Nielsen, John E., Petersen, Jørgen Holm, Juul, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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.
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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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