Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene.

P. F. Bouvagnet, E. E. Strehler, G. E. White, M. A. Strehler-Page, B. Nadal-Ginard, V. Mahdavi

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

To identify the DNA sequences that regulate the expression of the sarcomeric myosin heavy-chain (MHC) genes in muscle cells, a series of deletion constructs of the rat embryonic MHC gene was assayed for transient expression after introduction into myogenic and nonmyogenic cells. The sequences in 1.4 kilobases of 5'-flanking DNA were found to be sufficient to direct expression of the MHC gene constructs in a tissue-specific manner (i.e., in differentiated muscle cells but not in undifferentiated muscle and nonmuscle cells). Three main distinct regulatory domains have been identified: (i) the upstream sequences from positions -1413 to -174, which determine the level of expression of the MHC gene and are constituted of three positive regulatory elements and two negative ones; (ii) a muscle-specific regulatory element from positions -173 to -142, which restricts the expression of the MHC gene to muscle cells; and (iii) the promoter region, downstream from position -102, which directs transcription initiation. Introduction of the simian virus 40 enhancer into constructs where subportions of or all of the upstream sequences are deleted (up to position -173) strongly increases the level of expression of such truncated constructs but without changing their muscle specificity. These upstream sequences, which can be substituted for by the simian virus 40 enhancer, function in an orientation-, position-, and promoter-dependent fashion. The muscle-specific element is also promoter specific but does not support efficient expression of the MHC gene. The MHC promoter in itself is not muscle specific. These results underline the importance of the concerted action of multiple regulatory elements that are likely to represent targets for DNA-binding-regulatory proteins.

Original languageEnglish (US)
Pages (from-to)4377-4389
Number of pages13
JournalMolecular and Cellular Biology
Volume7
Issue number12
StatePublished - Dec 1987
Externally publishedYes

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Myosin Heavy Chains
Muscle Cells
Genes
Muscles
Simian virus 40
DNA-Binding Proteins
Genetic Promoter Regions
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Bouvagnet, P. F., Strehler, E. E., White, G. E., Strehler-Page, M. A., Nadal-Ginard, B., & Mahdavi, V. (1987). Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene. Molecular and Cellular Biology, 7(12), 4377-4389.

Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene. / Bouvagnet, P. F.; Strehler, E. E.; White, G. E.; Strehler-Page, M. A.; Nadal-Ginard, B.; Mahdavi, V.

In: Molecular and Cellular Biology, Vol. 7, No. 12, 12.1987, p. 4377-4389.

Research output: Contribution to journalArticle

Bouvagnet, PF, Strehler, EE, White, GE, Strehler-Page, MA, Nadal-Ginard, B & Mahdavi, V 1987, 'Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene.', Molecular and Cellular Biology, vol. 7, no. 12, pp. 4377-4389.
Bouvagnet, P. F. ; Strehler, E. E. ; White, G. E. ; Strehler-Page, M. A. ; Nadal-Ginard, B. ; Mahdavi, V. / Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene. In: Molecular and Cellular Biology. 1987 ; Vol. 7, No. 12. pp. 4377-4389.
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