TY - JOUR
T1 - Dimerization and DNA-binding properties of the transcription factor ΔFosB
AU - Jorissen, Helena J.M.M.
AU - Ulery, Paula G.
AU - Henry, Lisa
AU - Gourneni, Sreekrishna
AU - Nestler, Eric J.
AU - Rudenko, Gabby
PY - 2007/7/17
Y1 - 2007/7/17
N2 - The transcription factor, ΔFosB, 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 ΔFosB induction in animal models of several psychiatric and neurologic disorders. Fos family proteins, including ΔFosB, 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 ΔFosB 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 ΔFosB accumulates to abnormally elevated protein levels in highly specific regions of the brain in response to chronic stimulation, functional homodimers of ΔFosB are formed with the potential to uniquely regulate patterns of gene expression and thereby contribute to the complex processes of neural and behavioral adaptation.
AB - The transcription factor, ΔFosB, 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 ΔFosB induction in animal models of several psychiatric and neurologic disorders. Fos family proteins, including ΔFosB, 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 ΔFosB 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 ΔFosB accumulates to abnormally elevated protein levels in highly specific regions of the brain in response to chronic stimulation, functional homodimers of ΔFosB are formed with the potential to uniquely regulate patterns of gene expression and thereby contribute to the complex processes of neural and behavioral adaptation.
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U2 - 10.1021/bi700494v
DO - 10.1021/bi700494v
M3 - Article
C2 - 17580968
AN - SCOPUS:34447534398
SN - 0006-2960
VL - 46
SP - 8360
EP - 8372
JO - Biochemistry
JF - Biochemistry
IS - 28
ER -