Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-4-15
pubmed:abstractText
Although the cardiac homeobox gene Csx/Nkx-2.5 is essential for normal heart development, little is known about its regulatory mechanisms. In a search for the downstream target genes of Csx/Nkx-2. 5, we found that the atrial natriuretic peptide (ANP) gene promoter was strongly transactivated by Csx/Nkx-2.5. Deletion and mutational analyses of the ANP promoter revealed that the Csx/Nkx-2.5-binding element (NKE2) located at -240 was required for high level transactivation by Csx/Nkx-2.5. We also found that Csx/Nkx-2.5 and GATA-4 displayed synergistic transcriptional activation of the ANP promoter, and in contrast to previous reports (Durocher, D., Charron, F., Warren, R., Schwartz, R. J., and Nemer, M. (1997) EMBO J. 16, 5687-5696; Lee, Y., Shioi, T., Kasahara, H., Jobe, S. M., Wiese, R. J., Markham, B., and Izumo, S (1998) Mol. Cell. Biol. 18, 3120-3129), this synergism was dependent on binding of Csx/Nkx-2.5 to NKE2, but not on GATA-4-DNA interactions. Although GATA-4 also potentiated the Csx/Nkx-2.5-induced transactivation of the artificial promoter that contains multimerized Csx/Nkx-2.5-binding sites, Csx/Nkx-2.5 reduced the GATA-4-induced transactivation of the GATA-4-dependent promoters. These findings indicate that the cooperative transcriptional regulation mediated by Csx/Nkx-2.5 and GATA-4 is promoter context-dependent and suggest that the complex cis-trans interactions may fine-tune gene expression in cardiac myocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8231-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10075728-Animals, pubmed-meshheading:10075728-Binding Sites, pubmed-meshheading:10075728-DNA, pubmed-meshheading:10075728-DNA-Binding Proteins, pubmed-meshheading:10075728-Drug Synergism, pubmed-meshheading:10075728-GATA4 Transcription Factor, pubmed-meshheading:10075728-Gene Expression Regulation, Developmental, pubmed-meshheading:10075728-Heart, pubmed-meshheading:10075728-Homeodomain Proteins, pubmed-meshheading:10075728-Humans, pubmed-meshheading:10075728-Mice, pubmed-meshheading:10075728-Myocardium, pubmed-meshheading:10075728-Promoter Regions, Genetic, pubmed-meshheading:10075728-Rats, pubmed-meshheading:10075728-Sequence Analysis, DNA, pubmed-meshheading:10075728-Transcription, Genetic, pubmed-meshheading:10075728-Transcription Factors, pubmed-meshheading:10075728-Transcriptional Activation
pubmed:year
1999
pubmed:articleTitle
Context-dependent transcriptional cooperation mediated by cardiac transcription factors Csx/Nkx-2.5 and GATA-4.
pubmed:affiliation
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't