The molecular biology of the CCAAT-binding factor NF-Y

Mantovani, Roberto

doi:10.1016/s0378-1119(99)00368-6

Cited by 786 publications

(746 citation statements)

References 107 publications

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“…These results, in agreement with the luciferase experiments ( Figure 3c and Supplementary Figure S3), demonstrate that NF-Y contributes both to the expression and to the p53 regulation of Cdc25B. To test whether the reduced binding of NF-Y on the Cdc25B promoter observed after induction of p53 interferes with the recruitment of coactivators, we performed ChIP experiments as above, using anti-histone acetyltransferase p300, a coactivator known to interact with NF-Y (Mantovani, 1999). Results show that, while p300 was bound on the Cdc25B promoter in EJp53 uninduced cells, a release of this factor was observed after induction of p53 (Figure 4c).…”

Section: Resultssupporting

confidence: 83%

Cdc25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors

et al. 2011

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Cdc25B phosphatases function as key players in G2/M cell cycle progression by activating the CDK1-cyclinB1 complexes. They also have an essential role in recovery from the G2/M checkpoint activated in response to DNA damage. Overexpression of Cdc25B results in bypass of the G2/M checkpoint and illegitimate entry into mitosis, and also causes replicative stress, leading to genomic instability. Thus, fine-tuning of Cdc25B expression level is critical for correct cell cycle progression and G2 checkpoint recovery. However, the transcriptional regulation of Cdc25B remains largely unknown. Earlier studies have shown that the tumor suppressor p53 overexpression transcriptionally represses Cdc25B; however, the molecular mechanism of this repression has not yet been elucidated, although it was suggested to occur through the induction of p21. Here we show that Cdc25B is downregulated by the basal level of p53 in multiple cell types. This downregulation also occurs in p21À/À cell lines, indicating that p21 is not required for p53-mediated regulation of Cdc25B. Deletion and mutation analyses of the Cdc25B promoter revealed that downregulation by p53 is dependent on the presence of functional Sp1/Sp3 and NF-Y binding sites. Furthermore, chromatin immunoprecipitation analyses show that p53 binds to the Cdc25B promoter and mediates transcriptional attenuation through the Sp1 and NF-Y transcription factors. Our results suggest that the inability to downregulate Cdc25B after loss of p53 might contribute to tumorigenesis.

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Section: Resultssupporting

confidence: 83%

Cdc25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors

et al. 2011

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“…The Y box binds the heterotrimeric transcription factor, NF-Y, which consists of A, B and C subunits [10,11]. These transcription factors form a multiprotein complex, known as the MHC-II enhanceosome, which cooperatively binds the S-X-Y modules, and the multiprotein complex provides the appropriate interaction surface for recruiting the CIITA [12,13].…”

Section: Introductionmentioning

confidence: 99%

Direct role of NF‐κB activation in Toll‐like receptor‐triggered HLA‐DRA expression

Lee

Kim

et al. 2006

Eur J Immunol

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Microbial components, such as DNA containing immunostimulatory CpG motifs (CpG-DNA) and lipopolysaccharides (LPS), elicit the cell surface expression of MHC class II (MHC-II) through Toll-like receptor (TLR)/IL-1R. Here, we show that CpG-DNA and LPS induce expression of the HLA-DRA in the human B cell line, RPMI 8226. Ectopic expression of the dominant negative mutant of CIITA and RNA interference targeting the CIITA gene indicate that CIITA activation is not enough for the maximal MHC-II expression induced by CpG-DNA and LPS. Additionally, nuclear factor (NF)-jB activation is required for the CpG-DNA-activated and LPS-activated HLA-DRA expression, whereas IFN-c-induced MHC-II expression depends on CIITA rather than on NF-jB. Comprehensive mutant analyses, electrophoretic mobility shift assays and chromatin immunoprecipitation assays, reveal that the functional interaction of NF-jB with the promoter element is necessary for the TLR-mediated HLA-DRA induction by CpG-DNA and LPS. This novel mechanism provides the regulation of MHC-II gene expression with complexity and functional diversity.

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“…A search for putative NF‐Yb binding sites (CCAAT) within this region of the mouse genome identified three such sequences (termed sites 1–3 in this article, Supporting Information Table S2). This region is located 3′ to the transcription start site (TSS) and so falls outside of the classic proximal promoter position associated with CCAAT elements (Mantovani, 1999). …”

Section: Resultsmentioning

confidence: 99%

NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

Begum

Otsu

Ahmed

et al. 2018

Glia

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Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic‐ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF‐Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF‐Yb is regulated by excitotoxicity. Excitotoxicity‐induced alterations in NF‐Yb binding are associated with changes in Gria4 transcription, while knockdown of NF‐Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalized and primary OPC reveal that RNAi and pharmacological disruption of NF‐Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans‐acting mechanism regulating Gria4, and identify the NF‐Y network as a potential source of pharmacological targets for promoting OPC survival.

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The molecular biology of the CCAAT-binding factor NF-Y

Cited by 786 publications

References 107 publications

Cdc25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors

Cdc25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors

Direct role of NF‐κB activation in Toll‐like receptor‐triggered HLA‐DRA expression

NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

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