Nucleic Acids Research, 2003, Vol. 31, No. 24 7165-7174
© 2003 Oxford University Press
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Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c
1 School of Biological Sciences, Seoul National University, Seoul 151-742, Korea, 2 Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA and 3 International Vaccine Institute, Seoul 151-742, Korea
*To whom correspondence should be addressed. Tel: +82 2 880 5852; Fax: +82 2 878 5852; Email: jaebkim{at}snu.ac.kr
Adipocyte determination and differentiation dependent factor 1 (ADD1)/sterol regulatory element binding protein isoform (SREBP1c) is a key transcription factor in fatty acid metabolism and insulin- dependent gene expression. Although its transcriptional and post-translational regulation has been extensively studied, its regulation by interacting proteins is not well understood. To identify cellular proteins that associate with ADD1/SREBP1c, we employed the yeast two-hybrid system with an adipocyte cDNA library. Using the N-terminal domain of ADD1/SREBP1c as bait, we identified Twist2 (also known as Dermo-1), a basic helixloophelix (bHLH) protein, as a novel ADD1/SREBP1c interacting protein. Over-expression of Twist2 strongly repressed the transcriptional activity of ADD1/SREBP1c, primarily by reducing its binding to target sequences. Inhibition of histone deacetylase (HDAC) activity with HDAC inhibitors relieved this repression. Our data suggest that physical interaction between Twist2 and ADD1/SREBP1c attenuates transcriptional activation by ADD1/SREBP1c by inhibiting its binding to DNA, and that this inhibition is at least partly dependent on chromatin modification by HDACs.
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