Enhanced serum response element binding activity correlates with down-regulation of c-fos mRNA expression in the rat brain following repeated cortical lesions.
Repeated lesions of rat cerebral cortex result in transient peaks in the level of the c-fos transcript, but after the second lesion, this peak is substantially diminished. Using this lesion paradigm, we have analyzed the participation of the c-fos promoter elements SRE and DSE in the regulation of c-fos transcription. Following a single lesion, SRE/DSE binding activity peaked at 2 h, subsequent to the maximal levels of c-fos mRNA and parallel to the peak of c-Fos protein. After a second lesion (reinduction), 4 h following the initial lesion, SRE/DSE binding activity peaked after only 30 min and was significantly higher than following the first lesion. Once again, this peak occurred after the peak of c-fos mRNA expression and parallel with the second peak of c-Fos protein expression. These results suggested that the SRE and DSE promoter elements participated in the induction and down-regulation of c-fos transcription in vivo and suggested the possible involvement of Fos protein in its own regulation. The ability of Fos/Fra proteins to participate in a transcriptional complex was confirmed in gel-shift experiments with an AP-1 element, and the biphasic trend of binding activity was observed. Supershift experiments were performed to directly determine whether Fos protein was participating in SRE and/or DSE transcriptional complexes. No alterations in the position or intensity of the shifted band were observed using Fos/Fra antiserum suggesting that Fos/Fra proteins could be involved in c-fos down-regulation through mechanisms other than direct participation in the SRE/DSE transcription complex.
Ivkovic
S
S
Department of Psychiatry, New York University Medical Center, NY 10016, USA.
Kanazir
S
S
Rakic
L
L
Ehrlich
M E
ME
Ruzdijic
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D015536:Down-Regulation; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats
D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger