Transactivation domains are not functionally conserved between vertebrate and invertebrate serum response factors.
The transcription factor serum response factor (SRF) regulates expression of growth factor-dependent genes and muscle-specific genes in vertebrates. Homologous factors regulate differentiation of some ectodermic tissues in invertebrates. To explore the molecular basis of these different physiological functions, the functionality of human, Drosophila melanogaster and Artemia franciscana SRFs in mammalian cells has been compared in this article. D. melanogaster and, to a lesser extend, A. franciscana SRF co-expression represses the activity of strong SRF-dependent promoters, such as those of the mouse c-fos and A. franciscana actin 403 genes. Domain-exchange experiments showed that these results can be explained by the absence of a transactivation domain, functional in mammalian cells, in D. melanogaster and A. franciscana SRFs. Both invertebrate SRFs can dimerize with endogenous mouse SRF through the conserved DNA-binding and dimerization domain. Co-expression of human and A. franciscana SRFs activate expression of weaker SRF-dependent promoters, such as those of the human cardiac alpha-actin gene or an A. franciscana actin 403 promoter where the SRF-binding site has been mutated. Mapping of A. franciscana SRF domains involved in transcriptional activation has shown that the conserved DNA-binding and dimerization domain is neccessary, but not sufficient, for promoter activation in mammalian cells.
Avila
Sonia
S
Insitituto de Investigaciones Biomédicas CSIC/UAM, C/Arturo Duperier, Madrid, Spain.
Casero
Marie-Carmen
MC
Fernandez-Cantón
Rocío
R
Sastre
Leandro
L
D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001156:Artemia / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007448:Invertebrates; D010449:Peptide Mapping; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D027602:Serum Response Element; D026362:Serum Response Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014714:Vertebrates
D000199:Actins; D011994:Recombinant Proteins; D026362:Serum Response Factor