Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals

Abstract In humans the expression of lactase changes during post-natal development, leading to phenotypes known as lactase persistence and non-persistence. Polymorphisms within the lactase gene (LCT) enhancer, in particular the −13910C > T, but also others, are linked to these phenotypes. We were...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Milena N. Leseva, Richard J. Grand, Hagen Klett, Melanie Boerries, Hauke Busch, Alexandra M. Binder, Karin B. Michels
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2de50f8af6c74389afa70cd5b6b411af
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2de50f8af6c74389afa70cd5b6b411af
record_format	dspace
spelling	oai:doaj.org-article:2de50f8af6c74389afa70cd5b6b411af2021-12-02T15:08:05ZDifferences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals10.1038/s41598-018-23957-42045-2322https://doaj.org/article/2de50f8af6c74389afa70cd5b6b411af2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23957-4https://doaj.org/toc/2045-2322Abstract In humans the expression of lactase changes during post-natal development, leading to phenotypes known as lactase persistence and non-persistence. Polymorphisms within the lactase gene (LCT) enhancer, in particular the −13910C > T, but also others, are linked to these phenotypes. We were interested in identifying dynamic mediators of LCT regulation, beyond the genotype at −13910C > T. To this end, we investigated two levels of lactase regulation in human intestinal samples obtained from New England children and adolescents of mixed European ancestry: differential expression of transcriptional regulators of LCT, and variations in DNA methylation, and their relation to phenotype. Variations in expression of CDX2, POU2F1, GATA4, GATA6, and HNF1α did not correlate with phenotype. However, an epigenome-wide approach using the Illumina Infinium HM450 bead chip identified a differentially methylated position in the LCT promoter where methylation levels are associated with the genotype at −13910C > T, the persistence/non-persistence phenotype and lactase enzymatic activity. DNA methylation levels at this promoter site and CpGs in the LCT enhancer are associated with genotype. Indeed, taken together they have a higher power to predict lactase phenotypes than the genotype alone.Milena N. LesevaRichard J. GrandHagen KlettMelanie BoerriesHauke BuschAlexandra M. BinderKarin B. MichelsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Milena N. Leseva Richard J. Grand Hagen Klett Melanie Boerries Hauke Busch Alexandra M. Binder Karin B. Michels Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
description	Abstract In humans the expression of lactase changes during post-natal development, leading to phenotypes known as lactase persistence and non-persistence. Polymorphisms within the lactase gene (LCT) enhancer, in particular the −13910C > T, but also others, are linked to these phenotypes. We were interested in identifying dynamic mediators of LCT regulation, beyond the genotype at −13910C > T. To this end, we investigated two levels of lactase regulation in human intestinal samples obtained from New England children and adolescents of mixed European ancestry: differential expression of transcriptional regulators of LCT, and variations in DNA methylation, and their relation to phenotype. Variations in expression of CDX2, POU2F1, GATA4, GATA6, and HNF1α did not correlate with phenotype. However, an epigenome-wide approach using the Illumina Infinium HM450 bead chip identified a differentially methylated position in the LCT promoter where methylation levels are associated with the genotype at −13910C > T, the persistence/non-persistence phenotype and lactase enzymatic activity. DNA methylation levels at this promoter site and CpGs in the LCT enhancer are associated with genotype. Indeed, taken together they have a higher power to predict lactase phenotypes than the genotype alone.
format	article
author	Milena N. Leseva Richard J. Grand Hagen Klett Melanie Boerries Hauke Busch Alexandra M. Binder Karin B. Michels
author_facet	Milena N. Leseva Richard J. Grand Hagen Klett Melanie Boerries Hauke Busch Alexandra M. Binder Karin B. Michels
author_sort	Milena N. Leseva
title	Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
title_short	Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
title_full	Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
title_fullStr	Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
title_full_unstemmed	Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals
title_sort	differences in dna methylation and functional expression in lactase persistent and non-persistent individuals
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2de50f8af6c74389afa70cd5b6b411af
work_keys_str_mv	AT milenanleseva differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT richardjgrand differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT hagenklett differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT melanieboerries differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT haukebusch differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT alexandrambinder differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals AT karinbmichels differencesindnamethylationandfunctionalexpressioninlactasepersistentandnonpersistentindividuals
_version_	1718388241130848256

Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals

Ejemplares similares