NF-kappaB site interacts with Sp factors and up-regulates the NR1 promoter during neuronal differentiation.
نویسندگان
چکیده
The NR1 gene undergoes induction in neurogenesis mainly via promoter de-repression, and up-regulation during neuronal differentiation by undefined mechanism(s). Here, we show that in the distal region the NR1 promoter has an active NF-kappaB site sharing the consensus with the immunoglobulin (Ig)/human immunodeficiency virus NF-kappaB site. Mutation of this site significantly reduced NR1 promoter up-regulation during neuronal differentiation of P19 cells. Electrophoretic mobility shift assays revealed that P19 nuclei constitutively contained p50 and that neuronal differentiation not only increased nuclear p50 but also induced p65 nuclear translocation. Responding to this change was an up-regulation of NF-kappaB-dependent promoter activity. However, inhibition of NF-kappaB nuclear translocation by an IkappaBalpha super-repressor or decoy DNA only moderately inhibited NR1 promoter up-regulation. Interestingly, the NR1 NF-kappaB site strongly interacted with Sp3/Sp1, instead of NF-kappaB factors, in P19 nuclear extracts. This interaction was reduced for Sp3 following neuronal differentiation, accompanied by dynamic expression of Sp factors. Cotransfection of Sp factors (Sp1, 3, or 4) upregulated the NR1 NF-kappaB site dramatically in differentiated neurons, but only moderately in undifferentiated P19 cells. This up-regulation was strong for Sp1 in differentiated cells and for Sp3 in undifferentiated cells. Chromatin-immunoprecipitation assays further demonstrated that Sp1 and Sp3 interacted with the NR1 NF-kappaB site in situ, and Sp3 lost its interaction after neuronal differentiation. We conclude that the NF-kappaB site positively regulates the NR1 promoter during neuronal differentiation via interacting mainly with Sp factors and neuronal differentiation reduces the effect of Sp3 factor on this site.
منابع مشابه
NF- B Site Interacts with Sp Factors and Up-regulates the NR1 Promoter during Neuronal Differentiation*
The NR1 gene undergoes induction in neurogenesis mainly via promoter de-repression, and up-regulation during neuronal differentiation by undefined mechanism(s). Here, we show that in the distal region the NR1 promoter has an active NFB site sharing the consensus with the immunoglobulin (Ig)/human immunodeficiency virus NFB site. Mutation of this site significantly reduced NR1 promoter up-regula...
متن کاملIkappaBalpha regulates Hes1 in osteoclast differentiation and resorption.
During osteoclast differentiation and resorption, both NF-kappaB and Notch signalling are activated. This study defines the mechanism about the influence of NFkappaB on Notch. To this end, IkappaBalphaM and Wild-type-IkappaBalpha were transfected into RAW 264.7 cells. The number of cells that differentiated into osteoclasts was quantified. The resorption area was measured. NF-kappaB transcripti...
متن کاملDownstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells.
The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs. In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice, a functional promoter region (-36 with respect to the transcription start site), a NF-kappaB...
متن کاملNFkappaB and Sp1 elements are necessary for maximal transcription of toll-like receptor 2 induced by Mycobacterium avium.
We have previously reported that Toll-like receptor (TLR) 2 mRNA was induced after infection with Mycobacterium avium. To investigate the molecular basis of TLR2 expression in macrophages, we cloned and analyzed the murine putative 5'-proximal promoter. Transient transfection of a 326-bp region from nucleotides -294-+32 relative to the first transcription start site was sufficient to induce max...
متن کاملPulmonary surfactant protein A regulates TLR expression and activity in human macrophages.
The pulmonary innate immune system responds to various airborne microbes. Although its specificity is broad and based on the recognition of pathogen-associated molecular patterns, it is uniquely regulated to limit inflammation and thereby prevent damage to the gas-exchanging alveoli. Macrophages, critical cell determinants of this system, recognize microbes through pattern recognition receptors...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 279 17 شماره
صفحات -
تاریخ انتشار 2004