Linked Life Data

17468179

Source:http://linkedlifedata.com/resource/pubmed/id/17468179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2007-7-2
pubmed:abstractText
Mutations in ZIC3 cause X-linked heterotaxy, a disorder characterized by abnormal lateralization of normally asymmetric thoracic and abdominal organs. Animal models demonstrate an early role for ZIC3 in embryonic left-right (LR) patterning. ZIC3 mutations have also been described in patients with isolated cardiovascular malformations. We wished to address the hypothesis that ZIC3 has plieotropic effects in development and may regulate cardiac development independent of its role in LR patterning. We observed significantly reduced expression of several markers of cardiac lineage commitment in Zic3(null/y) embryonic stem cells including atrial natriuretic factor (ANF), Nkx2.5 and Tbx5. Likewise, ANF expression-a molecular marker of trabecular myocardium and a direct target of multiple cardiac-specific transcription factors-was severely reduced in E9.5 Zic3 null hearts. Trabecular myocardium was reduced in these embryos. This finding was similar to that observed in embryos with cardiac-specific ablation of serum response factor (SRF), a direct transcriptional regulator of ANF expression. While ZIC3 by itself had no effect on the ANF promoter, it could bind to and inhibit a cardiac alpha-actin promoter through its zinc finger domains. We observed that ZIC3 could function as a coactivator of SRF on both cardiac alpha-actin and ANF promoters. The zinc fingers of ZIC3 and the mcm1, agamous deficiens SRF (MADS) box motif of SRF were found to mediate their physical and functional interactions. These findings reveal a novel role of ZIC3 in regulating cardiac gene expression and may explain, in part, the association of ZIC3 mutation with cardiovascular malformations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1649-60
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Identification of a novel role of ZIC3 in regulating cardiac development.
pubmed:affiliation
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural