Dimerization and DNA-binding properties of the transcription factor DeltaFosB.
The transcription factor, DeltaFosB, a splice isoform of fosB, accumulates in rodents in a brain-region-specific manner in response to chronic administration of drugs of abuse, stress, certain antipsychotic or antidepressant medications, electroconvulsive seizures, and certain lesions. Increasing evidence supports a functional role of such DeltaFosB induction in animal models of several psychiatric and neurologic disorders. Fos family proteins, including DeltaFosB, are known to heterodimerize with Jun family proteins to create active AP-1 transcription-factor complexes, which bind to DNA specifically at AP-1 consensus sites. We show here, using a range of biochemical and biophysical means, that recombinant, purified DeltaFosB forms homodimers as well, at concentrations less than 500 nM, and that these homodimers specifically bind to DNA oligonucleotides containing AP-1 consensus sequences in the absence of any Jun partner. Our results suggest that, as DeltaFosB accumulates to abnormally elevated protein levels in highly specific regions of the brain in response to chronic stimulation, functional homodimers of DeltaFosB are formed with the potential to uniquely regulate patterns of gene expression and thereby contribute to the complex processes of neural and behavioral adaptation.
Jorissen
Helena J M M
HJ
Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, USA.
Ulery
Paula G
PG
Henry
Lisa
L
Gourneni
Sreekrishna
S
Nestler
Eric J
EJ
Rudenko
Gabby
G
D000818:Animals; D002850:Chromatography, Gel; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D005454:Fluorescence Polarization; D051379:Mice; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014461:Ultracentrifugation
C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D004247:DNA