RGD Reference Report - Zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes. - Rat Genome Database

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Zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes.

Authors: Hata, L  Murakami, M  Kuwahara, K  Nakagawa, Y  Kinoshita, H  Usami, S  Yasuno, S  Fujiwara, M  Kuwabara, Y  Minami, T  Yamada, Y  Yamada, C  Nakao, K  Ueshima, K  Nishikimi, T  Nakao, K 
Citation: Hata L, etal., J Mol Cell Cardiol. 2011 Jun;50(6):972-81. doi: 10.1016/j.yjmcc.2011.01.017. Epub 2011 Jan 31.
RGD ID: 8554463
Pubmed: PMID:21284946   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2011.01.017   (Journal Full-text)

Neuron-restrictive silencer factor (NRSF) is a zinc-finger transcription factor that binds to specific DNA sequences (NRSE) to repress transcription. By down-regulating the transcription of its target genes, NRSF contributes to the regulation of various biological processes, including neuronal differentiation, carcinogenesis and cardiovascular homeostasis. We previously reported that NRSF regulates expression of the cardiac fetal gene program, and that attenuation of NRSF-mediated repression contributes to genetic remodeling in hearts under pathological conditions. The precise molecular mechanisms and signaling pathways via which NRSF activity is regulated in pathological conditions of the heart remain unclear, however. In this study, to search for regulators of NRSF, we carried out yeast two-hybrid screening using NRSF as bait and identified zinc-finger protein (Zfp) 90 as a novel NRSF-binding protein. NRSF and Zfp90 colocalized in the nucleus, with the zinc-finger DNA-binding domain of the former specifically interacting with the latter. Zfp90 inhibited the repressor activity of NRSF by inhibiting its binding to DNA, thereby derepressing transcription of NRSF-target genes. Knockdown of Zfp90 by siRNA led to reduced expression of NRSF-target fetal cardiac genes, atrial and brain natriuretic peptide genes, and conversely, overexpression of Zfp90 in ventricular myocardium resulted in significant increases in the expression of these genes. Notably, expression of Zfp90 mRNA was significantly upregulated in mouse and human hearts with chronic heart failure. Collectively, these results suggest that Zfp90 functions as a negative regulator of NRSF and contributes to genetic remodeling during the development of cardiac dysfunction.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zfp90Ratpositive regulation of DNA-templated transcription involved_inIMP PMID:21284946UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RestRatprotein binding enablesIPIUniProtKB:Q61967PMID:21284946UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rest  (RE1-silencing transcription factor)
Zfp90  (zinc finger protein 90)


Additional Information