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Article

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

1
Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland
2
Department of Human Epigenetics, Mossakowski Medical Research Centre, PAS, A. Pawinskiego 5, 02-106 Warsaw, Poland
3
Institute of Medical Science, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University in Warsaw, 01-938 Warsaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(1), 78; https://doi.org/10.3390/ijms22010078
Received: 16 December 2020 / Accepted: 21 December 2020 / Published: 23 December 2020
(This article belongs to the Section Molecular Biology)
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. View Full-Text
Keywords: dermal fibroblasts; aging; epigenetic drift; 5-hydroxymethylcytosine (5hmC); regions differentially hydroxymethylated with age (DHMRs); ten-eleven translocation methylcytosine dioxygenase (TET) enzymes dermal fibroblasts; aging; epigenetic drift; 5-hydroxymethylcytosine (5hmC); regions differentially hydroxymethylated with age (DHMRs); ten-eleven translocation methylcytosine dioxygenase (TET) enzymes
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MDPI and ACS Style

Kołodziej-Wojnar, P.; Borkowska, J.; Wicik, Z.; Domaszewska-Szostek, A.; Połosak, J.; Cąkała-Jakimowicz, M.; Bujanowska, O.; Puzianowska-Kuznicka, M. Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts. Int. J. Mol. Sci. 2021, 22, 78. https://doi.org/10.3390/ijms22010078

AMA Style

Kołodziej-Wojnar P, Borkowska J, Wicik Z, Domaszewska-Szostek A, Połosak J, Cąkała-Jakimowicz M, Bujanowska O, Puzianowska-Kuznicka M. Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts. International Journal of Molecular Sciences. 2021; 22(1):78. https://doi.org/10.3390/ijms22010078

Chicago/Turabian Style

Kołodziej-Wojnar, Paulina, Joanna Borkowska, Zofia Wicik, Anna Domaszewska-Szostek, Jacek Połosak, Marta Cąkała-Jakimowicz, Olga Bujanowska, and Monika Puzianowska-Kuznicka. 2021. "Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts" International Journal of Molecular Sciences 22, no. 1: 78. https://doi.org/10.3390/ijms22010078

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