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Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

Authors
  • Ueda, Kohei
  • Fujiki, Katsunori
  • Shirahige, Katsuhiko
  • Gomez-Sanchez, Celso E.
  • Fujita, Toshiro
  • Nangaku, Masaomi
  • Nagase, Miki1, 2, 3, 4, 2, 5, 6, 7, 8, 9, 10, 2, 11, 12
  • 1 Department of Nephrology and Endocrinology
  • 2 The University of Tokyo
  • 3 Research Center for Epigenetic Disease
  • 4 Institute of Molecular and Cellular Biosciences
  • 5 Endocrine Section
  • 6 G.V. (Sonny) Montgomery VA Medical Center
  • 7 Endocrinology
  • 8 University of Mississippi Medical Center
  • 9 Division of Clinical Epigenetics
  • 10 Research Center for Advanced Science and Technology
  • 11 Department of Anatomy and Life Structure
  • 12 School of Medicine Juntendo University
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publication Date
Jan 01, 2014
Volume
445
Issue
1
Pages
132–137
Identifiers
DOI: 10.1016/j.bbrc.2014.01.125
Source
Elsevier
Keywords
License
Unknown

Abstract

Background and objectiveMineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). MethodsWe analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10−7M aldosterone for 1h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7M aldosterone for 3h by microarray. Results3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. ConclusionsWe, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

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