Multiple interdependent regulatory sites in the mouse c-<i>fos</i>promoter determine basal level transcription: cell type-specific effects

Lucibello, Frances C.; Ehlert, F; Müller, Rolf

doi:10.1093/nar/19.13.3583

Cited by 23 publications

(9 citation statements)

References 49 publications

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“…Furthermore, triple helix modification at -431 by OR-IV caused a 70% decrease in CAT expression. This site is located within FBS3/AP-2 binding elements [36,371 and may be crucial in c-fos expression and cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

c‐fos Protooncogene Transcription can be Modulated by Oligonucleotide‐Mediated Formation of Triplex Structures in vitro

Lavrovsky¹,

Stoltz²,

Vlassov³

et al. 1996

European Journal of Biochemistry

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A homopurine . homopyrimidine sequence of the c:fos promoter was chosen as a target for a triple helix oligonucleotide. Eight DNA oligonucleotides that ranged from 14 to 31 bp were shown to form a triple helix with three sequences within the c-fos promoter region. Reactive derivatives of homopyrimidine oligonucleotides bearing the 5'-or 3'-terminal DNA alkylation aromatic 2-chloroethylamino group were also synthesized. It was concluded, based on the physical properties of the DNA oligonucleotide complex, that the oligonucleotide forms a colinear triplex with the duplex binding sites. We investigated in detail, using electrophoretic mobility and footprinting protection, whether such oligonucleotide . DNA complexes are of benefit in designing high-affinity probes for a natural DNA sequence in the mouse c-fos gene. Our results demonstrate that four different DNA targets within the c-fos promoter region can form triplex structures with synthetic oligonucleotides in a sequence-specific manner. Moreover, in vitro modifications of the retinoblastoma-gene-product-binding site of the cTfos promoter at position -83 in front of the cAMP/cAMP-responsive element binding site and fos-binding site 3/activator-protein-2-like (FBS3/AP-2-like) site at position -431 by triple helix forming oligonucleotides cause dramatic suppression of ,fox-chloramphenicol acetyltransferase activity in endothelial cells. These results provide a basis for the development of a specific oligonucleotide target forming triplex-DNA complex, and emphasize the importance of a target forming triplex as a basis for control of gene expression and cell proliferation.Keywords: cTfos ; triplex ; promoter ; transcription factor ; gene regulation, Intermolecular DNA triple helix formation offers the opportunity to achieve precise sequence recognition, and has a potential use in gene therapy [I, 21. The formation of a specific complex between two strands of polyuridylic acid and one strand of polyadenylic acid in the presence of divalent cations was first reported in 1957 131. Recent studies have revealed the site-specific formation of short intermolecular triplexes by a wide variety of techniques, which include different kinds of footprintings, affinity cleavage, and NMR [4-1 I]. Chemical and physical evidence indicates that the nucleotide bases of the third strand occupy the major groove of the Watson-Crick target duplex [12, 131. A triple helix in nucleic acid results from specific Hoogsteen-type or reverse Hoogsteen-type hydrogen-bonding interactions between bases in a homopurine strand of a Watson-Crick duplex and an additional third strand. Several DNA triplets have been characterized resulting in two distinct classes of structural motifs in DNA triplexes. In the case of pyrimidine . purine . pyrimidine (Y*RY) triplexes (so-called pyrimidine motif), the third pyrimidine-rich strand runs parallel to the purine strand of the target duplex resulting in the formation of T*AT and C+*GC base triple combinations [4, 6, 111. The requirement for protonation of the th...

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Section: Discussionmentioning

confidence: 99%

c‐fos Protooncogene Transcription can be Modulated by Oligonucleotide‐Mediated Formation of Triplex Structures in vitro

Lavrovsky¹,

Stoltz²,

Vlassov³

et al. 1996

European Journal of Biochemistry

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“…The SRF at the c‐ fos SRE is known to be activated by growth factors present in serum (Treisman 1986) and the CRE has been described as the major element regulating basal c‐ fos transcription (Lucibello et al . 1991).…”

Section: Effect Of Deletions or Mutations Of Cis‐acting Elements On Tmentioning

confidence: 99%

“…The SRF at the c-fos SRE is known to be activated by growth factors present in serum (Treisman 1986) and the CRE has been described as the major element regulating basal c-fos transcription (Lucibello et al 1991). Not unexpectedly, mutations at the SRE or CRE caused a significant decrease in the constitutive expression of these constructs compared with expression observed with the The cells were co-transfected with 100 ng Renilla luciferase plasmid and values on the y-axis represent the ratio between firefly and Renilla luciferase activities.…”

Section: Effect Of Deletions or Mutations Of Cis-acting Elements On Tmentioning

confidence: 99%

Activation of c‐fos by lipopolysaccharide in glial cells via p38 mitogen‐activated protein kinase‐dependent activation of serum or cyclic AMP/calcium response element

Simi

Edling

Ingelman‐Sundberg

et al. 2005

Journal of Neurochemistry

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Pathological conditions such as ischaemic stroke and inflammatory disorders cause c-fos activation in the brain. This activation contributes to the initiation of the brain's inflammatory response, orchestrated by activated glial cells. The inflammatory signalling cascades leading to c-fos activation in glial cells are not well characterized. Thus, we have attempted a detailed analysis of the cis-acting elements, transcription factors and upstream kinase pathways involved in the activation of c-fos by lipopolysaccharide (LPS) in primary rat cortical glial cells. We found that (1) LPS-induced c-fos mRNA levels were sensitive to p38 mitogen-activated protein kinase (MAPK) inhibitors but not to mitogen-activated/ extracellular signal-regulated kinase (ERK) or calciumcalmodulin-dependent kinase inhibitors, (2) LPS activated both serum response element (SRE) and cyclic AMP/calcium response element (CRE)-driven luciferase reporters in transient transfection assays, (3) LPS induced the phosphorylation of Elk1 CRE-binding protein (CREB)/activated transcription factor-1 (ATF-1) and the activation of GAL4-Elk1 and GAL4-CREB chimeric proteins, and (4) mutation of both SRE and CRE elements was necessary and sufficient to completely abolish LPS induction of a rat c-fos proximal promoter-luciferase reporter. Thus, c-fos activation by LPS in glial cells occurs via the SRE or CRE in an independent manner, and involves the Elk1 or CREB/ATF-1 transcription factors. Elk1-mediated transactivation was dependent on p38 MAPK, suggesting a crucial role of these factors in mediating inflammatory responses in the CNS. A plethora of physiological and pathological stimuli has been described to induce c-fos expression in the brain. Despite being an essential part of physiological brain activity, c-Fos has also been implicated in neuronal death, and studies with antisense oligonucleotides have suggested that inhibition of c-fos expression may be beneficial in cerebral ischaemia (Smeyne et al. 1993;Lu et al. 1997). Notably, glial c-Fos expression has been demonstrated in pathological conditions such as ischaemia (Yu et al. 1995), injury (Tchelingerian et al. 1997) and viral infection in the CNS (Rubio and Martin-Clemente 1999), as well as following peripheral infections as mimicked by systemic lipopolysaccharide (LPS) administration in rats (Matsunaga et al. 2001).Increasing evidence supports the role of glia-derived inflammatory mediators in both acute brain injury and neurodegenerative diseases, and interference with inflammatory gene expression has great therapeutic potential (Barone and Feuerstein 1999;Allan and Rothwell 2001

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“…These data suggest an in vivo requirement for CTF/NF1 or a CTF/NFl-like protein in regulating CSF-1 gene expression depends upon the availability of other irans-acting factors. The CTF/NF1 gene transcript undergoes alternative splicing to generate a family of three ubiquitously expressed transcription factors (Santoro et al, 1988) known to contribute to the basal activity of eukaryotic gene promoters, including the c-/os promoter (Lucibello et al, 1991), several liver-specific genes (Falquerho et al, 1992;Cuif et al, 1993), as well as the activity of several viral gene promoters (Jeang et al, 1987;Chong et al, 1991;Kumar et al, 1993). Activation of the mouse a(l) type I collagen promoter by transforming growth factor-ß requires the binding of CTF/NF1 or a CTF/NFl-like protein (Rossi et al, 1988), which suggests that CTF/NF1 may serve as a target for regulation by growth factors.…”

Section: Dna-binding Activity In Fibroblast Nuclear Extractsmentioning

confidence: 99%

Binding of a CTF/NF1-Like Protein to the Mouse Colony-Stimulating Factor-1 Gene Promoter

Konicek¹,

Xia²,

Harrington³

1995

DNA and Cell Biology

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Circulating and tissue-specific monocytes/macrophages, through production of hydrolytic enzymes and growth factors, can dramatically affect the local tissue environment. Colony-stimulating factor-1 (CSF-1) is a key regulator of monocyte/macrophage cell activity. CSF-1 is produced by stromal elements, including fibroblasts, which are found in all tissues. To understand at the molecular level how changes in CSF-1 gene transcription are initiated in fibroblasts, we set out to identify the cis-acting elements and cognate trans-acting factor(s) that bind regulatory regions of the mouse CSF-1 gene. Analysis of heterologous reporter constructs containing the mouse CSF-1 promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene in transiently transfected fibroblasts identified a cis-acting element located between base pairs -88 and -43 of the CSF-1 gene. Electrophoretic mobility-shift assays (EMSAs) and DNase I protection assays with nuclear extracts isolated from proliferating fibroblasts revealed distinct protein binding to the region spanning base pairs -90 to -68. Results from methylation interference assays suggest CTF/NF1 or a CTF/NF1-like factor is the cognate trans-acting factor. Mutation of the putative CTF/NF1 binding site in the CSF-1 promoter lead to a modest decrease in promoter activity in transiently transfected fibroblasts and monocytes. Therefore, we have demonstrated that CTF/NF1 or a CTF/NF1-like protein binds to the CSF-1 gene promoter; however, binding of the CTF/NF1-like protein alone does not significantly effect changes in CSF-1 gene promoter activity.

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Multiple interdependent regulatory sites in the mouse c-fospromoter determine basal level transcription: cell type-specific effects

Cited by 23 publications

References 49 publications

c‐fos Protooncogene Transcription can be Modulated by Oligonucleotide‐Mediated Formation of Triplex Structures in vitro

c‐fos Protooncogene Transcription can be Modulated by Oligonucleotide‐Mediated Formation of Triplex Structures in vitro

Activation of c‐fos by lipopolysaccharide in glial cells via p38 mitogen‐activated protein kinase‐dependent activation of serum or cyclic AMP/calcium response element

Binding of a CTF/NF1-Like Protein to the Mouse Colony-Stimulating Factor-1 Gene Promoter

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