Abstract
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 helix-loop-helix (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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
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CCAAT-Enhancer-Binding Proteins / chemistry*
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism*
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Cell Line
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Chromatin / metabolism
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Helix-Loop-Helix Motifs
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Histone Deacetylase Inhibitors
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Histones / metabolism
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Mice
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Protein Binding
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Protein Structure, Tertiary
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation / drug effects
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Twist-Related Protein 1
Substances
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CCAAT-Enhancer-Binding Proteins
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Chromatin
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DNA-Binding Proteins
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Histone Deacetylase Inhibitors
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Histones
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RNA, Messenger
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Repressor Proteins
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Srebf1 protein, mouse
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors
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Twist-Related Protein 1
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Twist2 protein, mouse
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DNA
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Histone Deacetylases