Genome-wide analysis of epigenetic signatures for kidney-specific transporters

Ryota Kikuchi, Shintaro Yagi, Hiroyuki Kusuhara, Satoki Imai, Yuichi Sugiyama, Kunio Shiota

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

DNA methylation-dependent gene silencing is one of the most characterized mechanisms in epigenetic regulation of gene expression. This process is thought to influence the ability of hepatocyte nuclear factor 1 (HNF1) to transactivate organic anion transporter expression in the liver and kidney. To evaluate this further we profiled 282 mouse solute carrier transporters by examining regions near their transcription start sites for tissue-dependent differentially methylated regions (T-DMR) using restriction tag-mediated amplification to determine T-DMR disparity between the liver and kidney. Forty-two of these were associated with T-DMR tags hypomethylated in the kidney but hypermethylated in the liver. Computational analysis found a canonical HNF1-binding motif within 1 kbp of the promoter region of 13 carriers including the amino acid transporters Slc6a19, Slc6a20, Slc7a8 and Slc7a9; all expressed predominantly in the kidney. Bisulfite genomic sequencing found that CpG dinucleotides neighboring the T-DMR tags were hypomethylated in the kidney compared with the liver. The Hnf1α promoter region itself contained a T-DMR hypomethylated in the liver and kidney but hypermethylated in the cerebrum, consistent with the tissue distribution of Hnf1α. Taken together, our results show a central role of DNA methylation in the kidney-specific expression of amino acid transporters thus determining both the tissue distribution of their master regulator, Hnf1α, and its interaction with downstream genes.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalKidney International
Volume78
Issue number6
DOIs
Publication statusPublished - 2010 Sep
Externally publishedYes

Fingerprint

Epigenomics
Genome
Kidney
Hepatocyte Nuclear Factor 1
Liver
Amino Acid Transport Systems
Tissue Distribution
DNA Methylation
Genetic Promoter Regions
Organic Anion Transporters
Transcription Initiation Site
Cerebrum
Gene Expression Regulation
Gene Silencing
Genes

Keywords

  • amino-acid transporter
  • DNA methylation
  • hepatocyte nuclear factor 1
  • SLC transporter
  • tissue-dependent differentially methylated region
  • tissue-specific expression

ASJC Scopus subject areas

  • Nephrology

Cite this

Kikuchi, R., Yagi, S., Kusuhara, H., Imai, S., Sugiyama, Y., & Shiota, K. (2010). Genome-wide analysis of epigenetic signatures for kidney-specific transporters. Kidney International, 78(6), 569-577. https://doi.org/10.1038/ki.2010.176

Genome-wide analysis of epigenetic signatures for kidney-specific transporters. / Kikuchi, Ryota; Yagi, Shintaro; Kusuhara, Hiroyuki; Imai, Satoki; Sugiyama, Yuichi; Shiota, Kunio.

In: Kidney International, Vol. 78, No. 6, 09.2010, p. 569-577.

Research output: Contribution to journalArticle

Kikuchi, R, Yagi, S, Kusuhara, H, Imai, S, Sugiyama, Y & Shiota, K 2010, 'Genome-wide analysis of epigenetic signatures for kidney-specific transporters', Kidney International, vol. 78, no. 6, pp. 569-577. https://doi.org/10.1038/ki.2010.176
Kikuchi R, Yagi S, Kusuhara H, Imai S, Sugiyama Y, Shiota K. Genome-wide analysis of epigenetic signatures for kidney-specific transporters. Kidney International. 2010 Sep;78(6):569-577. https://doi.org/10.1038/ki.2010.176
Kikuchi, Ryota ; Yagi, Shintaro ; Kusuhara, Hiroyuki ; Imai, Satoki ; Sugiyama, Yuichi ; Shiota, Kunio. / Genome-wide analysis of epigenetic signatures for kidney-specific transporters. In: Kidney International. 2010 ; Vol. 78, No. 6. pp. 569-577.
@article{6ec7636287af4038b6d81f37b936fe80,
title = "Genome-wide analysis of epigenetic signatures for kidney-specific transporters",
abstract = "DNA methylation-dependent gene silencing is one of the most characterized mechanisms in epigenetic regulation of gene expression. This process is thought to influence the ability of hepatocyte nuclear factor 1 (HNF1) to transactivate organic anion transporter expression in the liver and kidney. To evaluate this further we profiled 282 mouse solute carrier transporters by examining regions near their transcription start sites for tissue-dependent differentially methylated regions (T-DMR) using restriction tag-mediated amplification to determine T-DMR disparity between the liver and kidney. Forty-two of these were associated with T-DMR tags hypomethylated in the kidney but hypermethylated in the liver. Computational analysis found a canonical HNF1-binding motif within 1 kbp of the promoter region of 13 carriers including the amino acid transporters Slc6a19, Slc6a20, Slc7a8 and Slc7a9; all expressed predominantly in the kidney. Bisulfite genomic sequencing found that CpG dinucleotides neighboring the T-DMR tags were hypomethylated in the kidney compared with the liver. The Hnf1α promoter region itself contained a T-DMR hypomethylated in the liver and kidney but hypermethylated in the cerebrum, consistent with the tissue distribution of Hnf1α. Taken together, our results show a central role of DNA methylation in the kidney-specific expression of amino acid transporters thus determining both the tissue distribution of their master regulator, Hnf1α, and its interaction with downstream genes.",
keywords = "amino-acid transporter, DNA methylation, hepatocyte nuclear factor 1, SLC transporter, tissue-dependent differentially methylated region, tissue-specific expression",
author = "Ryota Kikuchi and Shintaro Yagi and Hiroyuki Kusuhara and Satoki Imai and Yuichi Sugiyama and Kunio Shiota",
year = "2010",
month = "9",
doi = "10.1038/ki.2010.176",
language = "English",
volume = "78",
pages = "569--577",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Genome-wide analysis of epigenetic signatures for kidney-specific transporters

AU - Kikuchi, Ryota

AU - Yagi, Shintaro

AU - Kusuhara, Hiroyuki

AU - Imai, Satoki

AU - Sugiyama, Yuichi

AU - Shiota, Kunio

PY - 2010/9

Y1 - 2010/9

N2 - DNA methylation-dependent gene silencing is one of the most characterized mechanisms in epigenetic regulation of gene expression. This process is thought to influence the ability of hepatocyte nuclear factor 1 (HNF1) to transactivate organic anion transporter expression in the liver and kidney. To evaluate this further we profiled 282 mouse solute carrier transporters by examining regions near their transcription start sites for tissue-dependent differentially methylated regions (T-DMR) using restriction tag-mediated amplification to determine T-DMR disparity between the liver and kidney. Forty-two of these were associated with T-DMR tags hypomethylated in the kidney but hypermethylated in the liver. Computational analysis found a canonical HNF1-binding motif within 1 kbp of the promoter region of 13 carriers including the amino acid transporters Slc6a19, Slc6a20, Slc7a8 and Slc7a9; all expressed predominantly in the kidney. Bisulfite genomic sequencing found that CpG dinucleotides neighboring the T-DMR tags were hypomethylated in the kidney compared with the liver. The Hnf1α promoter region itself contained a T-DMR hypomethylated in the liver and kidney but hypermethylated in the cerebrum, consistent with the tissue distribution of Hnf1α. Taken together, our results show a central role of DNA methylation in the kidney-specific expression of amino acid transporters thus determining both the tissue distribution of their master regulator, Hnf1α, and its interaction with downstream genes.

AB - DNA methylation-dependent gene silencing is one of the most characterized mechanisms in epigenetic regulation of gene expression. This process is thought to influence the ability of hepatocyte nuclear factor 1 (HNF1) to transactivate organic anion transporter expression in the liver and kidney. To evaluate this further we profiled 282 mouse solute carrier transporters by examining regions near their transcription start sites for tissue-dependent differentially methylated regions (T-DMR) using restriction tag-mediated amplification to determine T-DMR disparity between the liver and kidney. Forty-two of these were associated with T-DMR tags hypomethylated in the kidney but hypermethylated in the liver. Computational analysis found a canonical HNF1-binding motif within 1 kbp of the promoter region of 13 carriers including the amino acid transporters Slc6a19, Slc6a20, Slc7a8 and Slc7a9; all expressed predominantly in the kidney. Bisulfite genomic sequencing found that CpG dinucleotides neighboring the T-DMR tags were hypomethylated in the kidney compared with the liver. The Hnf1α promoter region itself contained a T-DMR hypomethylated in the liver and kidney but hypermethylated in the cerebrum, consistent with the tissue distribution of Hnf1α. Taken together, our results show a central role of DNA methylation in the kidney-specific expression of amino acid transporters thus determining both the tissue distribution of their master regulator, Hnf1α, and its interaction with downstream genes.

KW - amino-acid transporter

KW - DNA methylation

KW - hepatocyte nuclear factor 1

KW - SLC transporter

KW - tissue-dependent differentially methylated region

KW - tissue-specific expression

UR - http://www.scopus.com/inward/record.url?scp=77956230102&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956230102&partnerID=8YFLogxK

U2 - 10.1038/ki.2010.176

DO - 10.1038/ki.2010.176

M3 - Article

C2 - 20555317

AN - SCOPUS:77956230102

VL - 78

SP - 569

EP - 577

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -