A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes.
Serum response factor and the (CC(A/T)(6)GG) (CArG) box interact to promote the transcription of c-fos and muscle genes; this tissue-specific activity may require co-regulators for serum response factor. The alpha(1) integrin promoter contains two cis-elements besides the CArG box: a TAAT sequence, a consensus binding site for homeoproteins, and a GATA-binding box. As a candidate TAAT-binding factor, we cloned an NK family homeobox gene, Nkx-3.2, which is expressed mainly in smooth muscle tissues and skeletal structures. Nkx-3.2, serum response factor, and GATA-6 were co-expressed only in the medial smooth muscle layer of arteries. These three transcription factors formed a complex with their corresponding cis-elements and cooperatively transactivated smooth muscle genes, including alpha(1) integrin, SM22alpha, and caldesmon. Cardiac muscle-specific members of the NK and GATA families exist, and the triad of Nkx-2.5, serum response factor, and GATA-4 also transactivated the cardiac atrial natriuretic factor gene, which contains a CArG-like box, a GATA-binding box, and an NK-binding element. Our findings demonstrate that smooth and cardiac muscle have a shared transcriptional machinery and that the GATA and NK families confer muscle specificity on the serum response factor/CArG interaction.
Nishida
Wataru
W
Department of Neuroscience (D13), Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita City, Osaka 565-0871, Japan.
Nakamura
Mako
M
Mori
Syunsuke
S
Takahashi
Masanori
M
Ohkawa
Yasuyuki
Y
Tadokoro
Satoko
S
Yoshida
Kenji
K
Hiwada
Kunio
K
Hayashi
Ken'ichiro
K
Sobue
Kenji
K
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D050993:GATA6 Transcription Factor; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D039423:Integrin alpha1; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D026362:Serum Response Factor / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D015703:Antigens, CD; D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D039423:Integrin alpha1; D008840:Microfilament Proteins; D009124:Muscle Proteins; C107965:Nkx3-2 protein, mouse; D018075:RNA, Complementary; D012333:RNA, Messenger; D026362:Serum Response Factor; C058992:Tagln protein, mouse; D014157:Transcription Factors; C051615:transgelin; D003850:Deoxyribonuclease I