title: A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2) protein represses GATA4-dependent transcription.
abstract: GATA4 is a transcriptional activator of cardiac-restricted promoters and is required for normal cardiac morphogenesis. Friend of GATA-2 (FOG-2) is a multizinc finger protein that associates with GATA4 and represses GATA4-dependent transcription. To better understand the transcriptional repressor activity of FOG-2 we performed a functional analysis of the FOG-2 protein. The results demonstrated that 1) zinc fingers 1 and 6 of FOG-2 are each capable of interacting with evolutionarily conserved motifs within the N-terminal zinc finger of mammalian GATA proteins, 2) a nuclear localization signal (RKRRK) (amino acids 736-740) is required to program nuclear targeting of FOG-2, and 3) FOG-2 can interact with the transcriptional co-repressor, C-terminal-binding protein-2 via a conserved sequence motif in FOG-2 (PIDLS). Surprisingly, however, this interaction with C-terminal-binding protein-2 is not required for FOG-2-mediated repression of GATA4-dependent transcription. Instead, we have identified a novel N-terminal domain of FOG-2 (amino acids 1-247) that is both necessary and sufficient to repress GATA4-dependent transcription. This N-terminal repressor domain is functionally conserved in the related protein, Friend of GATA1. Taken together, these results define a set of evolutionarily conserved mechanisms by which FOG proteins repress GATA-dependent transcription and thereby form the foundation for genetic studies designed to elucidate the role of FOG-2 in cardiac development.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Svensson
authors.forename: G S
authors.initials: GS
authors.lastname: Huggins
authors.forename: F B
authors.initials: FB
authors.lastname: Dardik
authors.forename: C E
authors.initials: CE
authors.lastname: Polk
authors.forename: J M
authors.initials: JM
authors.lastname: Leiden
mesh_terms: D016475:3T3 Cells; D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D050485:GABA Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019913:Nuclear Localization Signals; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D000429:Alcohol Oxidoreductases; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050485:GABA Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D019913:Nuclear Localization Signals; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; C079264:Slc6a11 protein, mouse; C492170:Zfpm2 protein, mouse; C096794:C-terminal binding protein