title: Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c.
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.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyoung Ho
authors.initials: HH
authors.lastname: Lee
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.forename: Eung Jae
authors.initials: EJ
authors.lastname: Yoo
authors.forename: Carlotta A
authors.initials: CA
authors.lastname: Glackin
authors.forename: Young Il
authors.initials: YI
authors.lastname: Choi
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Rho Hyun
authors.initials: RH
authors.lastname: Seong
authors.forename: Sang Dai
authors.initials: SD
authors.lastname: Park
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D051879:Twist-Related Protein 1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012333:RNA, Messenger; D012097:Repressor Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C096852:Twist2 protein, mouse; D004247:DNA; D006655:Histone Deacetylases