CpG island of rat sphingosine kinase-1 gene: Tissue-dependent DNA methylation status and multiple alternative first exons

Takuya Imamura, Jun Ohgane, Seiichiro Ito, Tomoya Ogawa, Naka Hattori, Satoshi Tanaka, Kunio Shiota

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

It is generally recognized that CpG islands are not methylated in normal tissues. SPHK1 is a key enzyme catalyzing the production of sphingosine 1-phosphate, a novel signaling molecule for the proliferation and differentiation of various cells, including neural cells. Sequencing of genomic DNA and cDNA reveals that rat Sphk1a consists of six exons encoding 383 amino acids. Furthermore, we identified six alternative first exons for mRNA subtypes (Sphk1a, -b, -c, -d, -e, and -f) within a 3.7-kb CpG island. The CpG island contains a tissue-dependent, differentially methylated region (T-DMR; ∼ 200 bp), which is located ∼ 800 bp upstream of the first exon of Sphk1a. T-DMR is hypomethylated in the adult brain where Sphk1a is expressed, whereas it is hypermethylated in the adult heart where the gene is not expressed. In fetal tissues, hypomethylation of T-DMR is not associated with expression of Sphk1a, which suggests that differential availability of transcription factors is also likely to be involved in the mechanism of its expression. Here, we identify rat Sphk1, using multiple alternative first exons for the subtypes, and demonstrate that there is a CpG island bearing T-DMR.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalGenomics
Volume76
Issue number1-3
DOIs
Publication statusPublished - 2001 Jul 15
Externally publishedYes

Keywords

  • Alternative splicing
  • Brain
  • CpG island
  • Development
  • DNA methylation
  • Sphingosine kinase
  • Tissue specific

ASJC Scopus subject areas

  • Genetics

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