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Lactase non-persistence is directed by DNA variation-dependent epigenetic aging
Inability to digest lactose due to lactase non-persistence is a common trait in adult mammals, with the exception of certain human populations that exhibit lactase persistence. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899171/ https://www.ncbi.nlm.nih.gov/pubmed/27159559 http://dx.doi.org/10.1038/nsmb.3227 |
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author | Labrie, Viviane Buske, Orion J Oh, Edward Jeremian, Richie Ptak, Carolyn Gasiūnas, Giedrius Maleckas, Almantas Petereit, Rūta Žvirbliene, Aida Adamonis, Kęstutis Kriukienė, Edita Koncevičius, Karolis Gordevičius, Juozas Nair, Akhil Zhang, Aiping Ebrahimi, Sasha Oh, Gabriel Šikšnys, Virginijus Kupčinskas, Limas Brudno, Michael Petronis, Arturas |
author_facet | Labrie, Viviane Buske, Orion J Oh, Edward Jeremian, Richie Ptak, Carolyn Gasiūnas, Giedrius Maleckas, Almantas Petereit, Rūta Žvirbliene, Aida Adamonis, Kęstutis Kriukienė, Edita Koncevičius, Karolis Gordevičius, Juozas Nair, Akhil Zhang, Aiping Ebrahimi, Sasha Oh, Gabriel Šikšnys, Virginijus Kupčinskas, Limas Brudno, Michael Petronis, Arturas |
author_sort | Labrie, Viviane |
collection | PubMed |
description | Inability to digest lactose due to lactase non-persistence is a common trait in adult mammals, with the exception of certain human populations that exhibit lactase persistence. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in some. We performed a comprehensive epigenetic study of the human and mouse intestine using chromosome-wide DNA modification profiling and targeted bisulfite sequencing. Epigenetically-controlled regulatory elements were found to account for the differences in lactase mRNA levels between individuals, intestinal cell types and species. The importance of these regulatory elements in modulating lactase mRNA levels was confirmed by CRISPR-Cas9-induced deletions. Genetic factors contribute to epigenetic changes occurring with age at the regulatory elements, as lactase persistence- and non-persistence-DNA haplotypes demonstrated markedly different epigenetic aging. Thus, genetic factors facilitate a gradual accumulation of epigenetic changes with age to affect phenotypic outcome. |
format | Online Article Text |
id | pubmed-4899171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48991712016-11-09 Lactase non-persistence is directed by DNA variation-dependent epigenetic aging Labrie, Viviane Buske, Orion J Oh, Edward Jeremian, Richie Ptak, Carolyn Gasiūnas, Giedrius Maleckas, Almantas Petereit, Rūta Žvirbliene, Aida Adamonis, Kęstutis Kriukienė, Edita Koncevičius, Karolis Gordevičius, Juozas Nair, Akhil Zhang, Aiping Ebrahimi, Sasha Oh, Gabriel Šikšnys, Virginijus Kupčinskas, Limas Brudno, Michael Petronis, Arturas Nat Struct Mol Biol Article Inability to digest lactose due to lactase non-persistence is a common trait in adult mammals, with the exception of certain human populations that exhibit lactase persistence. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in some. We performed a comprehensive epigenetic study of the human and mouse intestine using chromosome-wide DNA modification profiling and targeted bisulfite sequencing. Epigenetically-controlled regulatory elements were found to account for the differences in lactase mRNA levels between individuals, intestinal cell types and species. The importance of these regulatory elements in modulating lactase mRNA levels was confirmed by CRISPR-Cas9-induced deletions. Genetic factors contribute to epigenetic changes occurring with age at the regulatory elements, as lactase persistence- and non-persistence-DNA haplotypes demonstrated markedly different epigenetic aging. Thus, genetic factors facilitate a gradual accumulation of epigenetic changes with age to affect phenotypic outcome. 2016-05-09 2016-06 /pmc/articles/PMC4899171/ /pubmed/27159559 http://dx.doi.org/10.1038/nsmb.3227 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Labrie, Viviane Buske, Orion J Oh, Edward Jeremian, Richie Ptak, Carolyn Gasiūnas, Giedrius Maleckas, Almantas Petereit, Rūta Žvirbliene, Aida Adamonis, Kęstutis Kriukienė, Edita Koncevičius, Karolis Gordevičius, Juozas Nair, Akhil Zhang, Aiping Ebrahimi, Sasha Oh, Gabriel Šikšnys, Virginijus Kupčinskas, Limas Brudno, Michael Petronis, Arturas Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title | Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title_full | Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title_fullStr | Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title_full_unstemmed | Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title_short | Lactase non-persistence is directed by DNA variation-dependent epigenetic aging |
title_sort | lactase non-persistence is directed by dna variation-dependent epigenetic aging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899171/ https://www.ncbi.nlm.nih.gov/pubmed/27159559 http://dx.doi.org/10.1038/nsmb.3227 |
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