Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells

Jairo Rodriguez; Laura Vives; Mireia Jordà; Christina Morales Torres; Mar Muñoz; Elisenda Vendrell; Miguel A Peinado

doi:10.1093/nar/gkm1105

Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells

Jairo Rodriguez, Laura Vives, Mireia Jordà, Christina Morales Torres, Mar Muñoz, Elisenda Vendrell, Miguel A Peinado

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

83 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Feb

Originalsprog	Engelsk
Tidsskrift	Nucleic Acids Research
Vol/bind	36
Udgave nummer	3
Sider (fra-til)	770-84
Antal sider	14
ISSN	0305-1048
DOI	https://doi.org/10.1093/nar/gkm1105
Status	Udgivet - 2008

Bibliografisk note

Keywords: Alu Elements; Carcinoma; Cell Line, Tumor; Chromosomes, Human; Colon; Colorectal Neoplasms; Computational Biology; CpG Islands; DNA Methylation; Epigenesis, Genetic; Genome, Human; Genomics; Humans; Intestinal Mucosa; Polymerase Chain Reaction

Adgang til dokumentet

10.1093/nar/gkm1105

Citationsformater

@article{82f133a0e24111ddb5fc000ea68e967b,

title = "Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells",

abstract = "Methylation of the cytosine is the most frequent epigenetic modification of DNA in mammalian cells. In humans, most of the methylated cytosines are found in CpG-rich sequences within tandem and interspersed repeats that make up to 45% of the human genome, being Alu repeats the most common family. Demethylation of Alu elements occurs in aging and cancer processes and has been associated with gene reactivation and genomic instability. By targeting the unmethylated SmaI site within the Alu sequence as a surrogate marker, we have quantified and identified unmethylated Alu elements on the genomic scale. Normal colon epithelial cells contain in average 25 486 +/- 10 157 unmethylated Alu's per haploid genome, while in tumor cells this figure is 41 995 +/- 17 187 (P = 0.004). There is an inverse relationship in Alu families with respect to their age and methylation status: the youngest elements exhibit the highest prevalence of the SmaI site (AluY: 42%; AluS: 18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%; AluS: 3.1%, AluJ: 12%). Data are consistent with a stronger silencing pressure on the youngest repetitive elements, which are closer to genes. Further insights into the functional implications of atypical unmethylation states in Alu elements will surely contribute to decipher genomic organization and gene regulation in complex organisms.",

author = "Jairo Rodriguez and Laura Vives and Mireia Jord{\`a} and {Morales Torres}, Christina and Mar Mu{\~n}oz and Elisenda Vendrell and Peinado, {Miguel A}",

note = "Keywords: Alu Elements; Carcinoma; Cell Line, Tumor; Chromosomes, Human; Colon; Colorectal Neoplasms; Computational Biology; CpG Islands; DNA Methylation; Epigenesis, Genetic; Genome, Human; Genomics; Humans; Intestinal Mucosa; Polymerase Chain Reaction",

year = "2008",

doi = "10.1093/nar/gkm1105",

language = "English",

volume = "36",

pages = "770--84",

journal = "Nucleic Acids Research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells

AU - Rodriguez, Jairo

AU - Vives, Laura

AU - Jordà, Mireia

AU - Morales Torres, Christina

AU - Muñoz, Mar

AU - Vendrell, Elisenda

AU - Peinado, Miguel A

N1 - Keywords: Alu Elements; Carcinoma; Cell Line, Tumor; Chromosomes, Human; Colon; Colorectal Neoplasms; Computational Biology; CpG Islands; DNA Methylation; Epigenesis, Genetic; Genome, Human; Genomics; Humans; Intestinal Mucosa; Polymerase Chain Reaction

PY - 2008

Y1 - 2008

N2 - Methylation of the cytosine is the most frequent epigenetic modification of DNA in mammalian cells. In humans, most of the methylated cytosines are found in CpG-rich sequences within tandem and interspersed repeats that make up to 45% of the human genome, being Alu repeats the most common family. Demethylation of Alu elements occurs in aging and cancer processes and has been associated with gene reactivation and genomic instability. By targeting the unmethylated SmaI site within the Alu sequence as a surrogate marker, we have quantified and identified unmethylated Alu elements on the genomic scale. Normal colon epithelial cells contain in average 25 486 +/- 10 157 unmethylated Alu's per haploid genome, while in tumor cells this figure is 41 995 +/- 17 187 (P = 0.004). There is an inverse relationship in Alu families with respect to their age and methylation status: the youngest elements exhibit the highest prevalence of the SmaI site (AluY: 42%; AluS: 18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%; AluS: 3.1%, AluJ: 12%). Data are consistent with a stronger silencing pressure on the youngest repetitive elements, which are closer to genes. Further insights into the functional implications of atypical unmethylation states in Alu elements will surely contribute to decipher genomic organization and gene regulation in complex organisms.

AB - Methylation of the cytosine is the most frequent epigenetic modification of DNA in mammalian cells. In humans, most of the methylated cytosines are found in CpG-rich sequences within tandem and interspersed repeats that make up to 45% of the human genome, being Alu repeats the most common family. Demethylation of Alu elements occurs in aging and cancer processes and has been associated with gene reactivation and genomic instability. By targeting the unmethylated SmaI site within the Alu sequence as a surrogate marker, we have quantified and identified unmethylated Alu elements on the genomic scale. Normal colon epithelial cells contain in average 25 486 +/- 10 157 unmethylated Alu's per haploid genome, while in tumor cells this figure is 41 995 +/- 17 187 (P = 0.004). There is an inverse relationship in Alu families with respect to their age and methylation status: the youngest elements exhibit the highest prevalence of the SmaI site (AluY: 42%; AluS: 18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%; AluS: 3.1%, AluJ: 12%). Data are consistent with a stronger silencing pressure on the youngest repetitive elements, which are closer to genes. Further insights into the functional implications of atypical unmethylation states in Alu elements will surely contribute to decipher genomic organization and gene regulation in complex organisms.

U2 - 10.1093/nar/gkm1105

DO - 10.1093/nar/gkm1105

M3 - Journal article

C2 - 18084025

VL - 36

SP - 770

EP - 784

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 3

ER -