RGD Reference Report - The zinc finger and C-terminal domains of MTA proteins are required for FOG-2-mediated transcriptional repression via the NuRD complex. - Rat Genome Database

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The zinc finger and C-terminal domains of MTA proteins are required for FOG-2-mediated transcriptional repression via the NuRD complex.

Authors: Roche, AE  Bassett, BJ  Samant, SA  Hong, W  Blobel, GA  Svensson, EC 
Citation: Roche AE, etal., J Mol Cell Cardiol. 2008 Feb;44(2):352-60. Epub 2007 Nov 12.
RGD ID: 2326010
Pubmed: PMID:18067919   (View Abstract at PubMed)
PMCID: PMC2277079   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yjmcc.2007.10.023   (Journal Full-text)

FOG-2 is a transcriptional co-regulator that is required for cardiac morphogenesis as mice deficient in this factor die during mid-gestation of cardiac malformations. FOG-2 interacts with GATA4 to attenuate GATA4-dependent gene expression. The first 12 amino acids of FOG-2 (the FOG Repression Motif) are necessary to mediate this repression. To determine the mechanism by which the FOG Repression Motif functions, we identified 7 polypeptides from rat cardiac nuclear extracts that co-purified with a GST-FOG-2 fusion protein. All proteins identified are members of the NuRD nucleosome remodeling complex. Using in vitro binding and co-immunoprecipitation assays, we demonstrate that Metastasis-Associated proteins (MTA)-1, 2 and 3 and Retinoblastoma binding proteins RbAp46 and RbAp48 interact with FOG-2, but not with a mutant form of FOG-2 that is unable to repress transcription. Furthermore, we define a novel domain located in the C-terminal portion of MTA-1 that mediates the FOG-2/MTA-1 interaction. We also demonstrate that knockdown of MTA protein expression dramatically impairs the ability of FOG-2 to repress GATA4 activity. Finally, we show that the zinc finger domain of MTA-1 is required for FOG-2-mediated transcriptional repression and that this domain interacts with RbAp46 and RbAp48 subunits of the NuRD complex. Together, these results demonstrate the importance of FOG-2/MTA/RbAp interactions for FOG-2-mediated transcriptional repression and further define the molecular interactions between the FOG Repression Motif and the NuRD complex.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Mta1  (metastasis associated 1)
Mta2  (metastasis associated 1 family, member 2)
Zfpm2  (zinc finger protein, multitype 2)

Objects referenced in this article
Gene Rbbp4 RB binding protein 4, chromatin remodeling factor Rattus norvegicus
Gene Rbbp7 RB binding protein 7, chromatin remodeling factor Rattus norvegicus

Additional Information