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Titolo:
REGULATION OF THE HUMAN CARDIAC SLOW-TWITCH TROPONIN-C GENE BY MULTIPLE, COOPERATIVE, CELL-TYPE-SPECIFIC, AND MYOD-RESPONSIVE ELEMENTS
Autore:
CHRISTENSEN TH; PRENTICE H; GAHLMANN R; KEDES L;
Indirizzi:
UNIV SO CALIF,SCH MED,INST GENET MED LOS ANGELES CA 90033 UNIV SO CALIF,SCH MED,INST GENET MED LOS ANGELES CA 90033 UNIV SO CALIF,SCH MED,DEPT BIOCHEM LOS ANGELES CA 90033 UNIV SO CALIF,SCH MED,DEPT MED LOS ANGELES CA 90033
Titolo Testata:
Molecular and cellular biology
fascicolo: 11, volume: 13, anno: 1993,
pagine: 6752 - 6765
SICI:
0270-7306(1993)13:11<6752:ROTHCS>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCLE-SPECIFIC ENHANCER; ALPHA-ACTIN PROMOTER; LOOP-HELIX PROTEINS; MYOGENIC DETERMINATION FACTORS; UBIQUITOUS NUCLEAR PROTEINS; POLYMERASE CHAIN-REACTION; CREATINE-KINASE GENE; RAT MYOCARDIAL-CELLS; BOX BINDING-FACTOR; SKELETAL-MUSCLE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
114
Recensione:
Indirizzi per estratti:
Citazione:
T.H. Christensen et al., "REGULATION OF THE HUMAN CARDIAC SLOW-TWITCH TROPONIN-C GENE BY MULTIPLE, COOPERATIVE, CELL-TYPE-SPECIFIC, AND MYOD-RESPONSIVE ELEMENTS", Molecular and cellular biology, 13(11), 1993, pp. 6752-6765

Abstract

The cardiac troponin C (cTnC) gene produces identical transcripts in slow-twitch skeletal muscle and in heart muscle (R. Gahlmann, R. Wade,P. Gunning, and L. Kedes, J. Mol. Biol. 201:379-391, 1988). A separate gene encodes the fast-twitch skeletal muscle troponin C and is not expressed in heart muscle. We have used transient transfection to characterize the regulatory elements responsible for skeletal and cardiac cell-type-specific expression of the human cTnC (HcTnC) gene. At least four separate elements cooperate to confer tissue-specific expression of this gene in differentiated myotubes; a basal promoter (between -61and -13) augments transcription 9-fold, upstream major regulatory sequences (between -68 and -142 and between -1319 and -4500) augment transcription as much as 39-fold, and at least two enhancer-like elements in the first intron (between +58 and +1028 and between +1029 and +1523) independently augment transcription 4- to 5-fold. These enhancers inthe first intron increase myotube-specific chloramphenicol acetyltransferase activity when linked to their own promoter elements or to the heterologous simian virus 40 promoter, and the effects are multiplicative rather than additive. Each of the major myotube regulatory regionsis capable of responding directly or indirectly to the myogenic determination factor, MyoD. A MyoD expression vector in 10T1/2 cells induced constructs carrying either the upstream HcTnC promoter elements or the first intron of the gene 300- to 500-fold. Expression was inhibitedby cotransfection with Id, a negative regulator of basic helix-loop-helix transcription factors. The basal promoter contains five tandem TGGGC repeats that interact with Spl or an Spl-like factor in nuclear extracts. Mutational analysis of this element demonstrated that two of the five repeat sequences were sufficient to support basal level musclecell-specific transcription. Whereas the basal promoter is also critical for expression in cardiac myocytes, the elements upstream of -67 appear to play little or no role. Major augmentation of expression in cardiomyocytes is also provided by sequences in the first intron, but these are upstream (between +58 and +1028). The downstream segment of the first intron has no enhancer activity in cardiomyocytes. A specificDNA-protein complex is formed by this C2 cell enhancer with extracts from C2 cells but not cardiomyocytes. These observations suggest that tissue-specific expression of the HcTnC gene is cooperatively regulated by the complex interactions of multiple regulatory elements and thatdifferent elements are used to regulate expression in myogenic and cardiac cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 03:43:23