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Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts

5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22–35 years and 74–94 years. Global quantit...

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Autores principales: Kołodziej-Wojnar, Paulina, Borkowska, Joanna, Wicik, Zofia, Domaszewska-Szostek, Anna, Połosak, Jacek, Cąkała-Jakimowicz, Marta, Bujanowska, Olga, Puzianowska-Kuznicka, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794952/
https://www.ncbi.nlm.nih.gov/pubmed/33374812
http://dx.doi.org/10.3390/ijms22010078
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author Kołodziej-Wojnar, Paulina
Borkowska, Joanna
Wicik, Zofia
Domaszewska-Szostek, Anna
Połosak, Jacek
Cąkała-Jakimowicz, Marta
Bujanowska, Olga
Puzianowska-Kuznicka, Monika
author_facet Kołodziej-Wojnar, Paulina
Borkowska, Joanna
Wicik, Zofia
Domaszewska-Szostek, Anna
Połosak, Jacek
Cąkała-Jakimowicz, Marta
Bujanowska, Olga
Puzianowska-Kuznicka, Monika
author_sort Kołodziej-Wojnar, Paulina
collection PubMed
description 5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22–35 years and 74–94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes.
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spelling pubmed-77949522021-01-10 Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts Kołodziej-Wojnar, Paulina Borkowska, Joanna Wicik, Zofia Domaszewska-Szostek, Anna Połosak, Jacek Cąkała-Jakimowicz, Marta Bujanowska, Olga Puzianowska-Kuznicka, Monika Int J Mol Sci Article 5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22–35 years and 74–94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes. MDPI 2020-12-23 /pmc/articles/PMC7794952/ /pubmed/33374812 http://dx.doi.org/10.3390/ijms22010078 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kołodziej-Wojnar, Paulina
Borkowska, Joanna
Wicik, Zofia
Domaszewska-Szostek, Anna
Połosak, Jacek
Cąkała-Jakimowicz, Marta
Bujanowska, Olga
Puzianowska-Kuznicka, Monika
Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title_full Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title_fullStr Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title_full_unstemmed Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title_short Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts
title_sort alterations in the genomic distribution of 5hmc in in vivo aged human skin fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794952/
https://www.ncbi.nlm.nih.gov/pubmed/33374812
http://dx.doi.org/10.3390/ijms22010078
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