RGD Reference Report - Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C. - Rat Genome Database

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Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C.

Authors: Zang, MX  Li, Y  Xue, LX  Jia, HT  Jing, H 
Citation: Zang MX, etal., J Cell Biochem. 2004 Dec 15;93(6):1255-66.
RGD ID: 8554739
Pubmed: PMID:15486975   (View Abstract at PubMed)
DOI: DOI:10.1002/jcb.20225   (Journal Full-text)

An intricate array of cell-specific multiprotein complexes participate in programs of cell-specific gene expression through combinatorial interaction with different transcription factors and cofactors. The dHAND basic helix-loop-helix (bHLH) transcription factor, which is essential for heart development and extra embryonic structures, is thought to regulate cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted transcription factors such as GATA4 and NKX2.5. Here, we determine that dHAND also interacts with the myocyte enhancer binding factor-2c (MEF2C) protein, which belongs to MADS-box transcription factors and is essential for heart development. dHAND and MEF2C synergistically activated expression of the atrial naturetic peptide gene (ANP) in transfected HeLa cells. GST-pulldown and immunoprecipitation assay demonstrate that full-length MEF2C protein is able to interact with dHAND in vitro and in vivo, just like MEF2A and bHLH transcription factors MyoD in skeletal muscle cells. In addition, electrophoretic mobility shift assays (EMSAs) demonstrate that MEF2C and dHAND do not influence each other's DNA binding activity. Using chromatin immunoprecipitation (ChIP) analysis in H9c2 cells we show that dHAND interact with MEF2C to form protein complex and bind A/T sequence in promoter of ANP. Taken together with previous observations, these results suggest the existence of large multiprotein transcriptional complex with core DNA binding proteins that physically interact with other transcriptional factors to form favorable conformation to potentiate transcription.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hand2Ratheart development involved_inIEP PMID:15486975UniProt 
Mef2cRatheart development involved_inIEP PMID:15486975UniProt 
NppaRatheart development involved_inTAS PMID:15486975UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hand2Ratprotein binding enablesIPIUniProtKB:A0A096MJY4PMID:15486975UniProt 
Mef2cRatprotein binding enablesIPIUniProtKB:P61295PMID:15486975UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Hand2  (heart and neural crest derivatives expressed 2)
Mef2c  (myocyte enhancer factor 2C)
Nppa  (natriuretic peptide A)


Additional Information