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Obesity risk gene TMEM18 encodes a sequence-specific DNA-binding protein
Jaana M Jurvansuu1, Adrian Goldman
1Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Helsinki, Finland. jaana.jurvansuu@helsinki.fi
Plos One
|October 8, 2011
Summary
Transmembrane protein 18 (TMEM18) localizes to the nuclear membrane and binds DNA. This binding may repress gene transcription by bringing chromatin near the nuclear envelope.
Area of Science:
- Molecular biology
- Cell biology
- Genetics
Background:
- Transmembrane protein 18 (TMEM18) is linked to cell migration and obesity.
- The precise molecular function of TMEM18 remains largely undescribed.
Purpose of the Study:
- To elucidate the molecular function and cellular localization of Transmembrane protein 18 (TMEM18).
- To investigate the DNA-binding properties and transcriptional regulatory potential of TMEM18.
Main Methods:
- Cellular localization studies to determine where TMEM18 resides within the cell.
- DNA-binding assays to assess sequence specificity and the role of the C-terminus.
- Reporter gene assays to measure the effect of TMEM18 on gene expression.
Main Results:
- TMEM18 was found to localize to the nuclear membrane.
- TMEM18 exhibits sequence-specific DNA binding via its positively charged C-terminus, which also contains a nuclear localization signal.
- Increased TMEM18 levels suppressed transcription from a reporter vector containing the TMEM18 target sequence.
Conclusions:
- TMEM18 functions as a DNA-binding protein at the nuclear membrane.
- The perinuclear localization of TMEM18-bound DNA suggests a potential mechanism for transcriptional repression.
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