Interindividual differences in placental expression of the SLC22A2 (OCT2) gene: Relationship to epigenetic variations in the 5'-upstream regulatory region

Jumpei Saito, Takeshi Hirota, Naomi Kikunaga, Kenji Otsubo, Ichiro Ieiri

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Organic cation transporters (OCTs) mediate the transport of organic cations and some drugs (e.g., metformin and cimetidine). OCT1, OCT2, and OCT3 are located in the imprinting cluster of the insulin-like growth factor 2 receptor. It has been reported that OCT1 and OCT3 show a biallelic expression, whereas OCT2 undergoes maternal imprinting in the human placenta; however, a loss of the imprinting of OCT2 has recently been reported in some placental samples. This study investigated whether epigenetic mechanisms are involved in interindividual differences in the placental expression of OCT2. Because OCT2 mRNA levels were higher in biallelic samples than that in monoallelic samples, we compared the DNA methylation and chromatin modifications in the promoter regions. There was no remarkable difference in DNA methylation between the mono allelic samples and biallelic samples. In contrast, histone H3 acetylation (H3Ac) was increased in the biallelic samples. A significant negative correlation was observed between the trimethylation of lysine-9 on histone H3 (H3K9me3) and the OCT2 mRNA levels. Our results suggest that H3Ac plays a role in the allelic expression of OCT2. In addition, H3K9me3 in the OCT2 promoter may explain the interindividual differences in placental OCT2 mRNA levels.

Original languageEnglish
Pages (from-to)3875-3883
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number9
DOIs
Publication statusPublished - Jan 1 2011

Fingerprint

Nucleic Acid Regulatory Sequences
Epigenomics
DNA Methylation
Acetylation
Histones
Messenger RNA
Cations
Genes
Somatomedin Receptors
Metformin
Cimetidine
Genetic Promoter Regions
Placenta
Lysine
Chromatin
Mothers
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Interindividual differences in placental expression of the SLC22A2 (OCT2) gene : Relationship to epigenetic variations in the 5'-upstream regulatory region. / Saito, Jumpei; Hirota, Takeshi; Kikunaga, Naomi; Otsubo, Kenji; Ieiri, Ichiro.

In: Journal of Pharmaceutical Sciences, Vol. 100, No. 9, 01.01.2011, p. 3875-3883.

Research output: Contribution to journalArticle

@article{266b6ebeee3043d1b2cfc2e20331e397,
title = "Interindividual differences in placental expression of the SLC22A2 (OCT2) gene: Relationship to epigenetic variations in the 5'-upstream regulatory region",
abstract = "Organic cation transporters (OCTs) mediate the transport of organic cations and some drugs (e.g., metformin and cimetidine). OCT1, OCT2, and OCT3 are located in the imprinting cluster of the insulin-like growth factor 2 receptor. It has been reported that OCT1 and OCT3 show a biallelic expression, whereas OCT2 undergoes maternal imprinting in the human placenta; however, a loss of the imprinting of OCT2 has recently been reported in some placental samples. This study investigated whether epigenetic mechanisms are involved in interindividual differences in the placental expression of OCT2. Because OCT2 mRNA levels were higher in biallelic samples than that in monoallelic samples, we compared the DNA methylation and chromatin modifications in the promoter regions. There was no remarkable difference in DNA methylation between the mono allelic samples and biallelic samples. In contrast, histone H3 acetylation (H3Ac) was increased in the biallelic samples. A significant negative correlation was observed between the trimethylation of lysine-9 on histone H3 (H3K9me3) and the OCT2 mRNA levels. Our results suggest that H3Ac plays a role in the allelic expression of OCT2. In addition, H3K9me3 in the OCT2 promoter may explain the interindividual differences in placental OCT2 mRNA levels.",
author = "Jumpei Saito and Takeshi Hirota and Naomi Kikunaga and Kenji Otsubo and Ichiro Ieiri",
year = "2011",
month = "1",
day = "1",
doi = "10.1002/jps.22595",
language = "English",
volume = "100",
pages = "3875--3883",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Interindividual differences in placental expression of the SLC22A2 (OCT2) gene

T2 - Relationship to epigenetic variations in the 5'-upstream regulatory region

AU - Saito, Jumpei

AU - Hirota, Takeshi

AU - Kikunaga, Naomi

AU - Otsubo, Kenji

AU - Ieiri, Ichiro

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Organic cation transporters (OCTs) mediate the transport of organic cations and some drugs (e.g., metformin and cimetidine). OCT1, OCT2, and OCT3 are located in the imprinting cluster of the insulin-like growth factor 2 receptor. It has been reported that OCT1 and OCT3 show a biallelic expression, whereas OCT2 undergoes maternal imprinting in the human placenta; however, a loss of the imprinting of OCT2 has recently been reported in some placental samples. This study investigated whether epigenetic mechanisms are involved in interindividual differences in the placental expression of OCT2. Because OCT2 mRNA levels were higher in biallelic samples than that in monoallelic samples, we compared the DNA methylation and chromatin modifications in the promoter regions. There was no remarkable difference in DNA methylation between the mono allelic samples and biallelic samples. In contrast, histone H3 acetylation (H3Ac) was increased in the biallelic samples. A significant negative correlation was observed between the trimethylation of lysine-9 on histone H3 (H3K9me3) and the OCT2 mRNA levels. Our results suggest that H3Ac plays a role in the allelic expression of OCT2. In addition, H3K9me3 in the OCT2 promoter may explain the interindividual differences in placental OCT2 mRNA levels.

AB - Organic cation transporters (OCTs) mediate the transport of organic cations and some drugs (e.g., metformin and cimetidine). OCT1, OCT2, and OCT3 are located in the imprinting cluster of the insulin-like growth factor 2 receptor. It has been reported that OCT1 and OCT3 show a biallelic expression, whereas OCT2 undergoes maternal imprinting in the human placenta; however, a loss of the imprinting of OCT2 has recently been reported in some placental samples. This study investigated whether epigenetic mechanisms are involved in interindividual differences in the placental expression of OCT2. Because OCT2 mRNA levels were higher in biallelic samples than that in monoallelic samples, we compared the DNA methylation and chromatin modifications in the promoter regions. There was no remarkable difference in DNA methylation between the mono allelic samples and biallelic samples. In contrast, histone H3 acetylation (H3Ac) was increased in the biallelic samples. A significant negative correlation was observed between the trimethylation of lysine-9 on histone H3 (H3K9me3) and the OCT2 mRNA levels. Our results suggest that H3Ac plays a role in the allelic expression of OCT2. In addition, H3K9me3 in the OCT2 promoter may explain the interindividual differences in placental OCT2 mRNA levels.

UR - http://www.scopus.com/inward/record.url?scp=79960120536&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960120536&partnerID=8YFLogxK

U2 - 10.1002/jps.22595

DO - 10.1002/jps.22595

M3 - Article

C2 - 21523786

AN - SCOPUS:79960120536

VL - 100

SP - 3875

EP - 3883

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -