Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements.
Transcription control regions of eukaryotic genes contain multiple sequence elements proposed to function independently to regulate transcription. We developed transgenic mice carrying fos-lacZ fusion genes with clustered point mutations in each of several distinct regulatory sequences: the sis-inducible element, the serum response element, the fos AP-1 site, and the calcium/cAMP response element. Analysis of Fos-lacZ expression in the CNS and in cultured cells demonstrated that all of the regulatory elements tested were required in concert for tissue- and stimulus-specific regulation of the c-fos promoter. This implies that the regulation of c-fos expression requires the concerted action of multiple control elements that direct the assembly of an interdependent transcription complex.
Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
L M
LM
Robertson
T K
TK
Kerppola
M
M
Vendrell
D
D
Luk
R J
RJ
Smeyne
C
C
Bocchiaro
J I
JI
Morgan
T
T
Curran
D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D015870:Gene Expression; D005786:Gene Expression Regulation; D016762:Genes, fos; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007608:Kainic Acid; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000032:analysis; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013687:Telencephalon / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D018808:Transcription Factor AP-1; D001616:beta-Galactosidase; D007608:Kainic Acid