Transcriptional regulation of the cardiac myosin light chain 2 gene under normal and stress conditions

Transcriptional regulation of the cardiac myosin light chain 2 gene under normal and stress conditions

AJH-APRIL 1995-VOL.8, NO.4, PART 2 Thursday, May 18, 12:15 pm TRANSCRIPTIONAL REGULATION OF THE CARDIAC MYOSIN LIGHT CHAIN 2 GENE UNDER NORMAL AND ST...

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AJH-APRIL 1995-VOL.8, NO.4, PART 2

Thursday, May 18, 12:15 pm TRANSCRIPTIONAL REGULATION OF THE CARDIAC MYOSIN LIGHT CHAIN 2 GENE UNDER NORMAL AND STRESS CONDITIONS E. Mascareno, M. Dhar & MAQ Siddiqui Department ofAnatomy &Cell Biology SUNY at Brooklyn An activator sequence (IRE) was Identified In Iheflrsllntron of the chicken MLC2 gene via mulagenesls and Iranslent Iransfebtlon analysis of MLC2 recombinants In cardiac and skeletal muscle cells. Analysis of the DNA-binding proteins on gel mobility shift assay using iRE DNA as a probe showed alleast four ON!' ' :,dlng complexes. One of this complexes is competeci uut with excess of non-labelled upstream sequence CSS which IsInvolved in negative regUlation of MLC2 promoter, suggestfng that common protoins mediate both positive and negative regulallon of MLC2 gene. We have also obselVed Ihat the IRE bound protein complexes are developmentally regulated and modulated when cardiac cells are subjected to heat induced stress. An examination of IRE sequence revealed the presence 01 a conserved heat shock sequence (HSE) which Is also present in the promoter of the rat MLC2 gene. The HSE Is present in tiie promoters of several stress responsive genes, such as. those of heat shock proteins and Is necessary for activation of transcription Inthe response to stress. The HSE In MLC2 gene binds the heal shock factors (HSFS) in primary cardiac cells in culture follOWing heal shock trealment. MLC2 promoler/CAT reporter recombinants transfecled Into primary cardiac cells also respond positively upon heat shock treatment which is dependent upon an intact HSE. These results, therefore, suggest that the positive and negative regulatIon of MLC2 gene Is modulated through a complex mechanism involVing perhaps common proteins. which includes the Ubiquitous HSFs.

Key Words:

Hypertension,. stress', job stress

MOLECULAR BIOLOGY AND GENETICS 31A