Differential transcriptional control of the superoxide dismutase-2 kappaB element in neurons and astrocytes.
In addition to their conventional G-C/T target sequences, Sp1 family transcription factors (Sp-factors) can interact with a subset of the target sequences for NFkappaB. Due to the low level of bona fide NFkappaB activity in most resting cells, this interaction between Sp-factors and kappaB-sites could play important roles in cell function. Here we used mutagenesis of a canonical kappaB element from the immunoglobulin and HIV promoters to identify the GC-rich sequences at each end required for Sp-factor targeting. Through screening of multiple kappaB elements, a sequence element located in the second intron of superoxide dismutase-2 (SOD2) was identified as a good candidate for both NFkappaB and Sp-factor binding. In neurons, the prominent proteins interacting with this site were Sp3 and Sp4, whereas Sp1, Sp3, and NFkappaB were associated with this site in astroglia. The neuronal Sp-factors repressed transcriptional activity through this kappaB-site. In contrast, astroglial Sp-factors activated promoter activity through the same element. NFkappaB contributed to control of the SOD2 kappaB element only in astrocytes. These findings imply that cell-type specificity of transcription in the central nervous system, particularly with regard to kappaB elements, may include two unique aspects of neurons: 1) a recalcitrant NFkappaB and 2) the substitution of Sp4 for Sp1.
Mao
Xianrong
X
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Moerman-Herzog
Andréa M
AM
Wang
Wei
W
Barger
Steven W
SW
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000196:embryology; D002467:Cell Nucleus / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006678:HIV / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D051703:Sp Transcription Factors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D000099156:Superoxide Dismutase 2
D007136:Immunoglobulins; D016328:NF-kappa B; D051703:Sp Transcription Factors; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2