Developmental regulation and tissue-specific expression of the human muscle creatine kinase gene

J Biol Chem. 1988 Nov 15;263(32):17142-9.

Abstract

To define mechanisms regulating expression of M creatine kinase, the human gene including 5'-flanking DNA was cloned, characterized, and partially sequenced. The gene contains 8 exons interrupted by 7 introns spanning 17.5 kilobase pairs of DNA. The intron-exon splice sites were identified and conform to the GT-AG consensus rule. The TATA and CAAT boxes are located at positions -31 and -56 upstream of the transcription start site as determined by primer extension. The 5'-untranslated region is interrupted with the translation start codon located in the second exon. To determine whether sequences within the 5'-upstream DNA confer tissue-specific expression and developmental regulation, constructs containing 2620 base pairs of human M creatine kinase 5'-flanking DNA fused upstream of the chloramphenicol acetyltransferase gene in the promoterless plasmid pSVO-CAT were transfected into cultured C2C12 myoblasts. There was 17-fold induction of chloramphenicol acetyltransferase activity during differentiation as C2C12 myoblasts fused to form myotubes. The M creatine kinase fusion construct was not expressed in transfected nonmuscle cell lines, COS-7 and NIH/3T3. Thus, cis-acting sequences within 2620 base pairs of the cap site are sufficient to direct developmental regulation and tissue-specific expression of the human M creatine kinase gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Creatine Kinase / genetics*
  • Gene Expression Regulation*
  • Genes, Homeobox
  • Humans
  • Molecular Sequence Data
  • Muscles / enzymology*
  • Nucleotide Mapping

Substances

  • Creatine Kinase

Associated data

  • GENBANK/J04435
  • GENBANK/M21487
  • GENBANK/M21488
  • GENBANK/M21489
  • GENBANK/M21490
  • GENBANK/M21491
  • GENBANK/M21492
  • GENBANK/M21493
  • GENBANK/M21494