Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1994-7-18
pubmed:abstractText
The alpha-myosin heavy-chain (alpha-MHC) gene is the major structural protein in the adult rodent myocardium. Its expression is restricted to the heart by a complex interplay of trans-acting factors and their cis-acting sites. However, to date, the factors that have been shown to regulate expression of this gene have also been found in skeletal muscle cells. Recently, transcription factor GATA-4, which has a tissue distribution limited to the heart and endodermally derived tissues, was identified. We recently found two putative GATA-binding sites within the proximal enhancer of the alpha-MHC gene, suggesting that GATA-4 might regulate its expression. In this study, we establish that GATA-4 interacts with the alpha-MHC GATA sites to stimulate cardiac muscle-specific expression. Mutation of the GATA-4-binding sites either individually or together decreased activity by 50 and 88% in the adult myocardium, respectively. GATA-4-dependent enhancement of activity from a heterologous promoter was mediated through the alpha-MHC GATA sites. Coinjection of an alpha-MHC promoter construct with a GATA-4 expression vector permitted ectopic expression in skeletal muscle but not in fibroblasts. Thus, the lack of alpha-MHC expression in skeletal muscle correlates with a lack of GATA-4. GATA-4 DNA binding activity was significantly up-regulated in triiodothyronine- or retinoic acid-treated cardiomyocytes. Putative GATA-4-binding sites are also found in the regulatory regions of other cardiac muscle-expressed structural genes. This indicates a mechanism whereby triiodothyronine and retinoic acid can exert coordinate control of the cardiac phenotype through a trans-acting regulatory factor.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1379240, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1516833, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1532229, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1569934, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1690729, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1690918, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1714909, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1722208, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1793583, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1848675, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1849812, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-1939278, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2034660, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2249770, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2277065, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2296592, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2555064, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2674899, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2725678, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2808370, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2828167, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2841611, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2888758, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2889129, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-2967498, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3194193, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3405222, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3472199, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3624281, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3670292, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3742743, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3785189, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3821727, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-3945800, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-6246368, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-6327679, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-6585819, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-6960240, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8076520, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8321207, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8321208, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8366095, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8428936, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8449897, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8455608, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-8495550, http://linkedlifedata.com/resource/pubmed/commentcorrection/8007990-942051
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4947-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
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