Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11).

Gene ·Vol. 348 ·2005-03-28 ·Pages 123-34

Inoue S, Oishi M

Abstract

We have studied the effects of methylation of the promoter region on the expression of human synaptotagmin XI (syt11), a gene implicated in the onset of schizophrenia. Sequence analysis showed that cytosine residues not in the CpG sequence, but still within the promoter region of the gene, are partially methylated. The methylated cytosine residues are located in the mRNA-coding (minus) strand of the promoter region (mCmCTTmCTTmCmC). Gel mobility shift assays showed that when the cytosine residues are methylated, the binding activity of an Sp family protein, a transcription factor, to the region is significantly reduced. Furthermore, transient transcription assays using artificially methylated promoter sequences showed that methylation did reduce the expression of the reporter gene. The biological significance of the finding is discussed in respect to the effect of methylation of non-CpG sequences in promoter regions on gene expression.

MeSH Terms

Animals Base Sequence Binding Sites/genetics Binding, Competitive CHO Cells Calcium-Binding Proteins/genetics Cell Line Cell Line, Tumor CpG Islands/genetics Cricetinae Cricetulus Cytosine/metabolism DNA/chemistry,genetics,metabolism DNA Methylation DNA-Binding Proteins/metabolism Electrophoretic Mobility Shift Assay Gene Expression Regulation Humans Luciferases/genetics,metabolism Membrane Glycoproteins/genetics Molecular Sequence Data Nerve Tissue Proteins/genetics Oligonucleotides/genetics,metabolism Plasmids/genetics Polymerase Chain Reaction/methods Promoter Regions, Genetic/genetics Sequence Analysis, DNA Sp1 Transcription Factor/metabolism Sp3 Transcription Factor Sulfites/chemistry Synaptotagmins Transcription Factors/metabolism Transcription Initiation Site Transcription, Genetic/genetics Transfection

Chemicals

Calcium-Binding Proteins DNA-Binding Proteins Membrane Glycoproteins Nerve Tissue Proteins Oligonucleotides SYT11 protein, human Sp1 Transcription Factor Sulfites Transcription Factors Synaptotagmins Sp3 Transcription Factor Cytosine DNA Luciferases hydrogen sulfite

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Inoue Shinichi

Kazusa Research Institute, 2-6-7, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan. sinoue@kazusa.or.jp

Oishi Michio

Article Info

Journal

Gene

Abbr.

Gene

ISSN

0378-1119

DOI

10.1016/j.gene.2004.12.044

sinoue@kazusa.or.jp

Published

2005-03-28

Pages

123-34

Language

English

Region

Netherlands

NLM ID

7706761

Subset

External Links

PubMed source DOI: 10.1016/j.gene.2004.12.044 View journal details

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Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11).

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