Members of the Nuclear Factor 1 Family Reduce the Transcriptional Potential of the Nuclear Receptor LXRα Promoter

Steffensen, Knut R.; Holter, Elin; Tobin, Kari Anne R.; Leclerc, Suzanne; Gustafsson, Jan‐Åke; Guérin, Sylvain L.; Eskild, Winnie

doi:10.1006/bbrc.2001.6078

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…This may be important for the induction of LXR above a threshold necessary to regulate certain target genes 34 . Several transcription factors, such as the nuclear factor 1 (NF1), CCAAT/enhancer-binding proteins (C/EBPs), and glucocorticoid receptors (GRs) were shown to affect the transcriptional potential of the mouse LXRα promoter 35 36 37 . Further investigation is required to elucidate details of the direct and indirect mechanisms for STAT1-dependent induction of LXRα and LXRβ genes in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

Kim

Lim

Yoon³

et al. 2016

Sci Rep

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Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXRα and LXRβ and expression of their target genes were inhibited in BMDM from STAT1−/− mice or by the STAT1-specific inhibitor fludarabine. Gas6-induced STAT1 phosphorylation, LXR activation, and LXR target gene expression were inhibited in BMDM from Mer−/− mice or by inhibition of PI3K or Akt. Gas6-induced Akt phosphorylation was inhibited in BMDM from STAT1−/− mice or in the presence of fludarabine. Gas6-induced LXR activity was enhanced through an interaction between LXRα and STAT1 on the DNA promoter of Arg2. Additionally, we found that Gas6 inhibited lipopolysaccharide (LPS)-induced nitrite production in a STAT1 and LXR pathway-dependent manner in BMDM. Additionally, Mer-neutralizing antibody reduced LXR and Arg2 expression in lung tissue and enhanced NO production in bronchoalveolar lavage fluid in LPS-induced acute lung injury. Our data suggest the possibility that the Gas6-Mer-PI3K/Akt-STAT1-LXR-Arg2 pathway plays an essential role for resolving inflammatory response in acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

Kim

Lim

Yoon³

et al. 2016

Sci Rep

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“…We previously demonstrated that NFI has a negative influence on the activity directed by the rPARP-1 promoter but not because it possesses any intrinsic repressor function but rather because it competes with Sp1 for the availability of a promoter composite element that bears overlapping target sites for both these transcription factors [ 39 , 40 ]. Interestingly, members from the NFI family have been reported to be as efficient as repressors [ 40 , 91 , 92 ] than activators [ 93 , 94 ] of gene transcription. Besides, NFI sites have often been shown to be located close to, or overlapping with nearby Sp1 sites.…”

Section: Discussionmentioning

confidence: 99%

Regulation of poly(ADP-ribose) polymerase-1 (PARP-1) gene expression through the post-translational modification of Sp1: a nuclear target protein of PARP-1

et al. 2007

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Background: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that plays critical functions in many biological processes, including DNA repair and gene transcription. The main function of PARP-1 is to catalyze the transfer of ADP-ribose units from nicotinamide adenine dinucleotide (NAD + ) to a large array of acceptor proteins, which comprises histones, transcription factors, as well as PARP-1 itself. We have previously demonstrated that transcription of the PARP-1 gene essentially rely on the opposite regulatory actions of two distinct transcription factors, Sp1 and NFI. In the present study, we examined whether suppression of PARP-1 expression in embryonic fibroblasts derived from PARP-1 knockout mice (PARP-1 -/-) might alter the expression and/or DNA binding properties of Sp1 and NFI. We also explored the possibility that Sp1 or NFI (or both) may represent target proteins of PARP-1 activity.

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“…The large diversity of this family of proteins, for which 19 isoforms have been described to date [reviewed in (61)], rely on the fact that each individual NFI mRNA transcript is subjected to alternative splicing (33,62). Members from the NFI family have been shown to function either as repressors (35,46,56) or activators (63,64) of gene transcription. Through interactions with weak binding sites, NFI may also regulate gene expression by its ability to either cooperate or compete with many transcription factors (35,65).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells

Ouellet¹,

Vigneault

Lessard

et al. 2006

Nucleic Acids Research

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The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein–protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated at the transcriptional level. By conducting both ligation-mediated PCR (LMPCR) and chromatin immunoprecipitation (ChIP) in vivo, we identified a functional target site for the transcription factor, nuclear factor I (NFI), in the basal promoter from the p21 gene. Transfection of recombinant constructs bearing mutations in the p21 NFI site demonstrated that NFI acts as a repressor of p21 gene expression in various types of cultured cells. Inhibition of NFI in human skin fibroblasts through RNAi considerably increased p21 promoter activity suggesting that NFI is a key repressor of p21 transcription. Over-expression of each of the four NFI isoforms in HCT116 cells established that each of them contribute to various extend to the repression of the p21 gene. Most of all, over-expression of NFI-B in doxorubicin, growth-arrested HCT116 increased the proportion of cells in the S-phase of the cell cycle whereas NFI-A and NFI-X reduced it, thereby establishing a role for NFI in the cell cycle dependent expression of p21.

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Members of the Nuclear Factor 1 Family Reduce the Transcriptional Potential of the Nuclear Receptor LXRα Promoter

Cited by 10 publications

References 37 publications

Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

Regulation of poly(ADP-ribose) polymerase-1 (PARP-1) gene expression through the post-translational modification of Sp1: a nuclear target protein of PARP-1

Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells

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