H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

被引：102

作者：

Fernandez, Agustin F. ^{[1
]}

Bayon, Gustavo F. ^{[1
]}

Urdinguio, Rocio G. ^{[1
]}

Torano, Estela G. ^{[1
]}

Garcia, Maria G. ^{[1
]}

Carella, Antonella ^{[1
]}

Petrus-Reurer, Sandra ^{[1
]}

Ferrero, Cecilia ^{[1
]}

Martinez-Camblor, Pablo ^{[2
,3
]}

Cubillo, Isabel ^{[4
]}

Garcia-Castro, Javier ^{[4
]}

Delgado-Calle, Jesus ^{[5
]}

Perez-Campo, Flor M. ^{[5
]}

Riancho, Lose A.

Bueno, Clara ^{[6
]}

Menendez, Pablo ^{[6
,7
]}

Mentink, Anouk ^{[8
]}

Mareschi, Katia ^{[9
,10
]}

Claire, Fabian ^{[11
]}

Fagnani, Corrado ^{[12
]}

Medda, Emanuela ^{[12
]}

Toccaceli, Virgilia ^{[12
]}

Brescianini, Sonia

Moran, Sebastian ^{[13
]}

Esteller, Manel ^{[6
,13
,14
]}

Stolzing, Alexandra ^{[11
,15
]}

de Boer, Jan ^{[8
,16
]}

Nistico, Lorenza ^{[12
]}

Stazi, Maria A. ^{[12
]}

Fraga, Mario F. ^{[1
,17
]}

机构：

[1] Univ Oviedo, HUCA, Inst Oncol Asturias IUOPA, Canc Epigenet Lab, E-33006 Oviedo, Spain

[2] FICYT, OIB, Oviedo 33005, Spain

[3] Univ Autonoma Chile, Santiago, Chile

[4] Inst Salud Carlos III, Unidad Biotecnol Celular, Area Genet Humana, Madrid 28029, Spain

[5] Univ Cantabria, Hosp UM Valdecilla, IDIVAL, Dept Internal Med, Santander 39011, Spain

[6] Univ Barcelona, Sch Med, Josep Carreras Leukemia Res Inst, E-08036 Barcelona, Spain

[7] ICREA, Barcelona 08010, Spain

[8] Univ Twente, MIRA Inst Biomed Technol & Tech Med, NL-7500 AE Enschede, Netherlands

[9] Regina Margherita Childrens Hosp, Stem Cell Transplantat & Cellular Therapy Div, I-10126 Turin, Italy

[10] Univ Turin, Dept Publ Hlth & Pediat, I-10126 Turin, Italy

[11] Univ Leipzig, Translat Ctr Regenerat Med, D-04103 Leipzig, Germany

[12] Ist Super Sanita, Natl Ctr Epidemiol Surveillance & Hlth Promot, Genet Epidemiol Unit, I-00161 Rome, Italy

[13] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain

[14] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona 08036, Catalonia, Spain

[15] Univ Loughborough, Wolfson Sch Mech & Mfg Engn, Loughborough LE11 3TU, Leics, England

[16] Maastricht Univ, Merln Inst Technol Inspired Regenerat Med, CBITE Lab, NL-6200 MD Maastricht, Netherlands

[17] CSIC, CNB, Dept Immunol & Oncol, E-28049 Madrid, Spain

来源：

GENOME RESEARCH | 2015年 / 25卷 / 01期

关键词：

WHOLE-GENOME DATA; GENE-EXPRESSION; EPIGENETIC REGULATION; METHYLATION PROFILES; AGE; CANCER; TWINS; LANDSCAPE; REVEALS; ISLANDS;

D O I：

10.1101/gr.169011.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature ofDNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.

引用

页码：27 / 40

页数：14

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