Genomes and Genes
ccaat binding factor
Summary: A heterotrimeric DNA-binding protein that binds to CCAAT motifs in the promoters of eukaryotic genes. It is composed of three subunits: A, B and C.
- Peart M, Prives C. Mutant p53 gain of function: the NF-Y connection. Cancer Cell. 2006;10:173-4 pubmed..These data thereby implicate transcriptional activation by mutant p53 as a key mechanism responsible for its oncogenic activity. ..
- Ceribelli M, Alcalay M, Vigano M, Mantovani R. Repression of new p53 targets revealed by ChIP on chip experiments. Cell Cycle. 2006;5:1102-10 pubmed..Finally, there is a large overlap (66%) between p53 and NF-Y targets. Our data reinstate the physiological importance of p53 promoter recognition and direct transcriptional repression as a mechanism to cope with DNA-damage. ..
- Xu Y, Zhou Y, Luo W, Zhu Q, Levy D, MacDougald O, et al. NF-Y and CCAAT/enhancer-binding protein alpha synergistically activate the mouse amelogenin gene. J Biol Chem. 2006;281:16090-8 pubmed..These results suggest that C/EBPalpha and NF-Y synergistically activate the mouse amelogenin gene and can contribute to its physiological regulation during amelogenesis. ..
- Imbriano C, Gurtner A, Cocchiarella F, Di Agostino S, Basile V, Gostissa M, et al. Direct p53 transcriptional repression: in vivo analysis of CCAAT-containing G2/M promoters. Mol Cell Biol. 2005;25:3737-51 pubmed
- Caretti G, Salsi V, Vecchi C, Imbriano C, Mantovani R. Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters. J Biol Chem. 2003;278:30435-40 pubmed..These data indicate that following the release of E2Fs/HDACs, a hierarchy of PCAF-NF-Y-p300 interactions and H3-H4 acetylations are required for activation of cell-cycle promoters. ..
- Salsi V, Caretti G, Wasner M, Reinhard W, Haugwitz U, Engeland K, et al. Interactions between p300 and multiple NF-Y trimers govern cyclin B2 promoter function. J Biol Chem. 2003;278:6642-50 pubmed..Transient association to a weak site might be a point of regulation during the cell cycle and a general theme of multiple CCAAT box promoters. ..
- Chattopadhyay C, Hawke D, Kobayashi R, Maity S. Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and inhibits CBF-mediated transcription activation in vitro. Nucleic Acids Res. 2004;32:3632-41 pubmed..Altogether, our study identified p32 as a novel and specific corepressor of CBF-mediated transcription activation in vitro. ..
- Donati G, Gatta R, Dolfini D, Fossati A, Ceribelli M, Mantovani R. An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters. PLoS ONE. 2008;3:e2066 pubmed publisher..Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes. ..
- Di Agostino S, Strano S, Emiliozzi V, Zerbini V, Mottolese M, Sacchi A, et al. Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell. 2006;10:191-202 pubmed..Endogenous NF-Y, mutant p53, and p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant transcriptional regulation underlies the ability of mutant p53 proteins to act as oncogenic factors. ..
- Raghevendran V, Patil K, Olsson L, Nielsen J. Hap4 is not essential for activation of respiration at low specific growth rates in Saccharomyces cerevisiae. J Biol Chem. 2006;281:12308-14 pubmed
- Huang D, Kuo Y, Lai J, Suzuki Y, Sugano S, Chang Z. GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription of Gfi-1B gene. Nucleic Acids Res. 2004;32:3935-46 pubmed..Here we conclude that functional cooperation between GATA-1 and NF-Y contributes to erythroid-specific transcriptional activation of Gfi-1B promoter. ..
- Lee M, Kim S, Cho H, Lee K, Moon A, Jeong H, et al. Transcription factors NF-YA regulate the induction of human OGG1 following DNA-alkylating agent methylmethane sulfonate (MMS) treatment. J Biol Chem. 2004;279:9857-66 pubmed
- Yun J, Chae H, Choi T, Kim E, Bang Y, Chung J, et al. Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway. J Biol Chem. 2003;278:36966-72 pubmed..These results facilitate the elucidation of the regulatory mechanisms of cell cycle progression involving the p21-cdk2-NF-Y signaling pathway. ..
- Edwards D, Murray J, Smith A. Multiple genes encoding the conserved CCAAT-box transcription factor complex are expressed in Arabidopsis. Plant Physiol. 1998;117:1015-22 pubmed..The unexpected presence of multiple forms of each HAP homolog in Arabidopsis, compared with the single genes in yeast and vertebrates, suggests that the HAP2,3,5 complex may play diverse roles in gene transcription in higher plants. ..
- Steidl S, Hynes M, Brakhage A. The Aspergillus nidulans multimeric CCAAT binding complex AnCF is negatively autoregulated via its hapB subunit gene. J Mol Biol. 2001;306:643-53 pubmed..In the fungus Aspergillus nidulans the respective complex was designated AnCF (A. nidulans CCAAT binding factor). AnCF is composed of at least three subunits designated HapB, HapC and HapE...
- Coustry F, Hu Q, de Crombrugghe B, Maity S. CBF/NF-Y functions both in nucleosomal disruption and transcription activation of the chromatin-assembled topoisomerase IIalpha promoter. Transcription activation by CBF/NF-Y in chromatin is dependent on the promoter structure. J Biol Chem. 2001;276:40621-30 pubmed..It also suggests that specific promoter structure may play a role in the CBF-mediated transcription activation of nucleosomal topo IIalpha promoter template. ..
- Tüncher A, Spröte P, Gehrke A, Brakhage A. The CCAAT-binding complex of eukaryotes: evolution of a second NLS in the HapB subunit of the filamentous fungus Aspergillus nidulans despite functional conservation at the molecular level between yeast, A.nidulans and human. J Mol Biol. 2005;352:517-33 pubmed..nidulans hapB mutant was complemented, at least in part, by both the human NF-YA and S.cerevisiae Hap2p this finding suggests that the piggy-back mechanism of nuclear transport found for A.nidulans is conserved in yeast and human. ..
- Kam K, Jeong K, Norwitz E, Jorgensen E, Kaiser U. Oct-1 and nuclear factor Y bind to the SURG-1 element to direct basal and gonadotropin-releasing hormone (GnRH)-stimulated mouse GnRH receptor gene transcription. Mol Endocrinol. 2005;19:148-62 pubmed..In conclusion, NF-Y and Oct-1 bind to the SURG-1 element to direct basal and GnRH-stimulated expression of the mGnRHR gene. ..
- Duan Z, Stamatoyannopoulos G, Li Q. Role of NF-Y in in vivo regulation of the gamma-globin gene. Mol Cell Biol. 2001;21:3083-95 pubmed..These findings suggest that recruitment of NF-Y to the duplicated CCAAT box plays a role in the chromatin opening of the gamma gene promoter as well as in the communication between the gamma gene promoter and the LCR. ..
- Xing Y, Fikes J, Guarente L. Mutations in yeast HAP2/HAP3 define a hybrid CCAAT box binding domain. EMBO J. 1993;12:4647-55 pubmed..These findings suggest that short regions of HAP2 and HAP3 comprise a hybrid DNA-binding domain and that this domain can help hold the two subunits together in the CCAAT-binding complex. ..
- Magan N, Szremska A, Isaacs R, Stowell K. Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors. Biochem J. 2003;374:723-9 pubmed..Sp1 and NF-Y were both found to be transcriptional modulators with activator or repressor functions depending on protein/DNA context. Moreover, a functional interaction between Sp1 and NF-Y bound at proximal elements was observed. ..
- Janoo R, Neely L, Braun B, Whitehall S, Hoffman C. Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. Genetics. 2001;157:1205-15 pubmed..Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA. ..
- Morgan S, Beck W. Role of an inverted CCAAT element in human topoisomerase IIalpha gene expression in ICRF-187-sensitive and -resistant CEM leukemic cells. Mol Pharmacol. 2001;59:203-11 pubmed..This is the first study to show that topoIIalpha transcriptional up-regulation in ICRF-187-resistant cells is mediated in part by altered regulation of the third inverted CCAAT box in the topoIIalpha promoter. ..
- Benatti P, Basile V, Merico D, Fantoni L, Tagliafico E, Imbriano C. A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response. Nucleic Acids Res. 2008;36:1415-28 pubmed publisher..Our data highlight the importance of fine balancing the NF-Y-p53 duo for cell survival by (i) maintaining transcription of anti-apoptotic genes and (ii) preventing p53 activation that triggers the apoptotic cascade. ..
- Matuoka K, Chen K. Transcriptional regulation of cellular ageing by the CCAAT box-binding factor CBF/NF-Y. Ageing Res Rev. 2002;1:639-51 pubmed..In fact, the activities of NF-Y and E2F decrease during ageing and a dominant negative NF-YA induces SA-gal. Based on these observations, NF-Y appears to play an important role in the process of cellular ageing. ..
- Weidner G, Steidl S, Brakhage A. The Aspergillus nidulans homoaconitase gene lysF is negatively regulated by the multimeric CCAAT-binding complex AnCF and positively regulated by GATA sites. Arch Microbiol. 2001;175:122-32 pubmed..Results of Northern blot analysis also excluded that the global nitrogen regulator AreA is the responsible trans-acting GATA-binding factor. ..
- Wu G, Osada M, Guo Z, Fomenkov A, Begum S, Zhao M, et al. DeltaNp63alpha up-regulates the Hsp70 gene in human cancer. Cancer Res. 2005;65:758-66 pubmed..In addition, DeltaNp63alpha regulates transcription of the hsp70 gene through its interaction with the CCAAT binding factor and NF-Y transcription factors which are known to form a complex with the CCAAT box located in the hsp70 ..
- Matsui T, Katsuno Y, Inoue T, Fujita F, Joh T, Niida H, et al. Negative regulation of Chk2 expression by p53 is dependent on the CCAAT-binding transcription factor NF-Y. J Biol Chem. 2004;279:25093-100 pubmed..These results suggest that p53 negatively regulates Chk2 gene transcription through modulation of NF-Y function and that this regulation may be important for reentry of cells into the cell cycle after DNA damage is repaired. ..
- Chae H, Yun J, Bang Y, Shin D. Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for the expression of the cell cycle-regulatory genes and cell cycle G1/S and G2/M transitions. Oncogene. 2004;23:4084-8 pubmed..These results suggest that cdk2-dependent phosphorylation of NF-Y is essential for the expression of the cell cycle-regulatory genes and therefore for cell cycle progression at both G1/S and G2/M. ..
- Uramoto H, Wetterskog D, Hackzell A, Matsumoto Y, Funa K. p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF beta-receptor. J Cell Sci. 2004;117:5323-31 pubmed..These results suggest that p73 and DeltaNp73 behave as physiological regulators for the transcription of the PDGFRB promoter. ..
- Ru Lee W, Chen C, Liu S, Safe S. 17beta-estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non-genomic pathways. J Cell Biochem. 2006;99:209-20 pubmed..Thus, both genomic and non-genomic pathways of estrogen action are involved in induction of cdc25A in breast cancer cells. ..
- Hackzell A, Uramoto H, Izumi H, Kohno K, Funa K. p73 independent of c-Myc represses transcription of platelet-derived growth factor beta-receptor through interaction with NF-Y. J Biol Chem. 2002;277:39769-76 pubmed..Our results indicate that serum stimulation induces c-Myc and p73alpha, leading to the down-regulation of PDGF beta-receptor expression by repressing its transcription. ..
- Huang W, Zhao S, Ammanamanchi S, Brattain M, Venkatasubbarao K, Freeman J. Trichostatin A induces transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex. J Biol Chem. 2005;280:10047-54 pubmed..NF-Y.p300.PCAF.HDAC-1 multiprotein complex. Moreover, the interaction of NF-Y with the Sp1-associated complex may further explain why this specific Sp1 site mediates transcriptional responsiveness to TSA. ..
- Stephenson T, McIntyre C, Collet C, Xue G. Genome-wide identification and expression analysis of the NF-Y family of transcription factors in Triticum aestivum. Plant Mol Biol. 2007;65:77-92 pubmed..Organ-specific expression and differential response to drought indicate a plant-specific biological role for various members of this transcription factor family. ..
- Habib S, Riley D, Mahimainathan L, Bhandari B, Choudhury G, Abboud H. Tuberin regulates the DNA repair enzyme OGG1. Am J Physiol Renal Physiol. 2008;294:F281-90 pubmed..These data provide the first evidence that tuberin regulates a specific DNA repair enzyme, OGG1. This regulation may be important in the pathogenesis of kidney tumors in patients with TSC. ..
- Lok C, Lang A, Mirski S, Cole S. Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity: essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)-binding sites. Biochem J. 2002;368:741-51 pubmed..Our results suggest that the binding sites for NF-Y and Sp1 are critical for TOP2B transcription. ..
- Imbriano C, Bolognese F, Gurtner A, Piaggio G, Mantovani R. HSP-CBF is an NF-Y-dependent coactivator of the heat shock promoters CCAAT boxes. J Biol Chem. 2001;276:26332-9 pubmed..In yeast two-hybrid assays HSP-CBF interacts with NF-YB. These data implicate HSP-CBF as a non-DNA binding coactivator of heat shock genes that act on a DNA-bound NF-Y. ..
- Lascaris R, Bussemaker H, Boorsma A, Piper M, van der Spek H, Grivell L, et al. Hap4p overexpression in glucose-grown Saccharomyces cerevisiae induces cells to enter a novel metabolic state. Genome Biol. 2003;4:R3 pubmed..We show that overproduction of a single nuclear transcription factor enables cells to move to a novel state that displays features typical of, but clearly not identical to, other derepressed states. ..
- Krause K, Haugwitz U, Wasner M, Wiedmann M, MOssner J, Engeland K. Expression of the cell cycle phosphatase cdc25C is down-regulated by the tumor suppressor protein p53 but not by p73. Biochem Biophys Res Commun. 2001;284:743-50 pubmed..This reveals functional differences between p73 and p53 in regulating cell division. ..
- Steidl S, Tüncher A, Goda H, Guder C, Papadopoulou N, Kobayashi T, et al. A single subunit of a heterotrimeric CCAAT-binding complex carries a nuclear localization signal: piggy back transport of the pre-assembled complex to the nucleus. J Mol Biol. 2004;342:515-24 pubmed..This enables the cell to provide equimolar concentrations of all subunits to the nucleus. ..
- Ceribelli M, Dolfini D, Merico D, Gatta R, Vigano A, Pavesi G, et al. The histone-like NF-Y is a bifunctional transcription factor. Mol Cell Biol. 2008;28:2047-58 pubmed publisher..These data indicate that NF-Y is embedded in positive as well as in negative methyl histone marks, serving a dual function in transcriptional regulation, as an activator or as a repressor. ..
- Liang F, Schaufele F, Gardner D. Functional interaction of NF-Y and Sp1 is required for type a natriuretic peptide receptor gene transcription. J Biol Chem. 2001;276:1516-22 pubmed..Together, these studies show that NPR-A promoter activity is dominantly regulated through functional, and possibly physical, interactions of NF-Y and Sp1. ..
- Donati G, Imbriano C, Mantovani R. Dynamic recruitment of transcription factors and epigenetic changes on the ER stress response gene promoters. Nucleic Acids Res. 2006;34:3116-27 pubmed..These data highlight a previously unappreciated complexity of TFs binding and epigenetic changes, pointing to different TFs-specific pathways within this broad response. ..
- Benlhabib H, Herrera J. Expression of the Op18 gene is maintained by the CCAAT-binding transcription factor NF-Y. Gene. 2006;377:177-85 pubmed..These data suggest that NF-Y is a major transcription factor promoting expression of Op18. ..
- Joshi A, Wu Z, Reed R, Suttle D. Nuclear factor-Y binding to the topoisomerase IIalpha promoter is inhibited by both the p53 tumor suppressor and anticancer drugs. Mol Pharmacol. 2003;63:359-67 pubmed..The data presented points to the existence of both p53-dependent and -independent mechanisms for regulating NF-Y binding to ICBs in the topo IIalpha promoter and thus the modulation of topo IIalpha gene expression. ..
- Ben Naim O, Eshed R, Parnis A, Teper Bamnolker P, Shalit A, Coupland G, et al. The CCAAT binding factor can mediate interactions between CONSTANS-like proteins and DNA. Plant J. 2006;46:462-76 pubmed publisher..plant-specific CCT (CO, CO-like, TIMING OF CAB EXPRESSION 1) domain of both proteins binds the trimeric CCAAT binding factor (CBF) via its HAP5/NF-YC component...
- Gurtner A, Manni I, Fuschi P, Mantovani R, Guadagni F, Sacchi A, et al. Requirement for down-regulation of the CCAAT-binding activity of the NF-Y transcription factor during skeletal muscle differentiation. Mol Biol Cell. 2003;14:2706-15 pubmed..Thus, our results indicate that the suppression of NF-Y function is of crucial importance for the inhibition of several cell cycle genes and the induction of the early muscle-specific program in postmitotic muscle cells. ..
- Matuoka K, Yu Chen K. Nuclear factor Y (NF-Y) and cellular senescence. Exp Cell Res. 1999;253:365-71 pubmed..The regulation of thymidine kinase (TK) and dihydrofolate reductase (DHFR) genes in human diploid fibroblasts serves as an example of how NF-Y may have a role in replicative senescence by regulating age-dependent G1/S genes. ..
- Hortschansky P, Eisendle M, Al Abdallah Q, Schmidt A, Bergmann S, Thön M, et al. Interaction of HapX with the CCAAT-binding complex--a novel mechanism of gene regulation by iron. EMBO J. 2007;26:3157-68 pubmed..Remarkably, CBC-mediated regulation has an inverse impact on the expression of the same gene set in A. nidulans, compared with Saccharomyces cerevisae. ..
- Peng Y, Jahroudi N. The NFY transcription factor inhibits von Willebrand factor promoter activation in non-endothelial cells through recruitment of histone deacetylases. J Biol Chem. 2003;278:8385-94 pubmed..In endothelial cells, however, association of HDACs, NFY, and GATA6 is interrupted potentially through endothelial cell-specific signaling/mechanism, thus favoring the balance toward acetylation and activation of the VWF promoter. ..
- Khateb S, Weisman Shomer P, Hershco Shani I, Ludwig A, Fry M. The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA. Nucleic Acids Res. 2007;35:5775-88 pubmed..Taken together, our results suggest that secondary structures of (CGG)n in mRNA obstruct its translation and that quadruplex-disrupting proteins alleviate the translational block. ..
- Park S, Oh S, Lee M, Yoon S, Kim K, Kim J. CCAAT/enhancer binding protein and nuclear factor-Y regulate adiponectin gene expression in adipose tissue. Diabetes. 2004;53:2757-66 pubmed..These findings demonstrated that C/EBP and NF-Y are critical for the regulation of the adiponectin expression in response to nutrients and in the course of adipocyte differentiation. ..
- Goda H, Nagase T, Tanoue S, Sugiyama J, Steidl S, Tüncher A, et al. Nuclear translocation of the heterotrimeric CCAAT binding factor of Aspergillus oryzae is dependent on two redundant localising signals in a single subunit. Arch Microbiol. 2005;184:93-100 pubmed..nidulans. The nuclear translocation of the A. oryzae complex was found to be dependent on two redundant localising signals in HapB. ..
- Bhattacharya A, Deng J, Zhang Z, Behringer R, de Crombrugghe B, Maity S. The B subunit of the CCAAT box binding transcription factor complex (CBF/NF-Y) is essential for early mouse development and cell proliferation. Cancer Res. 2003;63:8167-72 pubmedTo understand the physiological function of the mammalian heterotrimeric CCAAT binding factor CBF, also known as NF-Y, we have generated a conditional Cbf-b mouse mutant by introducing loxP sites in the murine Cbf-b/Nf-ya gene...
- Zhu Q, Qian B, Levy D. CCAAT/enhancer-binding protein alpha (C/EBPalpha) activates transcription of the human microsomal epoxide hydrolase gene (EPHX1) through the interaction with DNA-bound NF-Y. J Biol Chem. 2004;279:29902-10 pubmed..C/EBPalpha-dependent EPHX1 activation was also supported by reconstitution studies in HeLa cells that lack this protein. These results establish that EPHX1 expression is regulated by C/EBPalpha interacting with DNA-bound NF-Y. ..
- Brons J, De Jong M, Valens M, Grivell L, Bolotin Fukuhara M, Blom J. Dissection of the promoter of the HAP4 gene in S. cerevisiae unveils a complex regulatory framework of transcriptional regulation. Yeast. 2002;19:923-32 pubmed
- Okamura H, Yoshida K, Sasaki E, Morimoto H, Haneji T. Transcription factor NF-Y regulates mdr1 expression through binding to inverted CCAAT sequence in drug-resistant human squamous carcinoma cells. Int J Oncol. 2004;25:1031-7 pubmed..NF-YA protein was expressed at higher levels in SCCTF cells than that in SCCKN cells. Hoechst dye staining also showed that MDR1 protein acts more effectively as an efflux pump in SCCTF cells than that in SCCKN cells. ..
- van Maris A, Bakker B, Brandt M, Boorsma A, Teixeira de Mattos M, Grivell L, et al. Modulating the distribution of fluxes among respiration and fermentation by overexpression of HAP4 in Saccharomyces cerevisiae. FEMS Yeast Res. 2001;1:139-49 pubmed..The effect of Hap4p overproduction was most drastic in aerobic, glucose-grown chemostat cultures in which ammonium was limiting. In such cultures, the biomass yield on glucose was double that of the wild-type. ..
- Kato M. An overview of the CCAAT-box binding factor in filamentous fungi: assembly, nuclear translocation, and transcriptional enhancement. Biosci Biotechnol Biochem. 2005;69:663-72 pubmed..In this review, the focus is on the CCAAT-box binding protein of filamentous fungi. The assembly, nuclear translocation, and transcriptional enhancement mechanisms of the CCAAT-box binding protein are discussed. ..
- Testa A, Donati G, Yan P, Romani F, Huang T, Vigano M, et al. Chromatin immunoprecipitation (ChIP) on chip experiments uncover a widespread distribution of NF-Y binding CCAAT sites outside of core promoters. J Biol Chem. 2005;280:13606-15 pubmed..The abundance of "unorthodox" CCAAT positions highlights an unexpected complexity of the NF-Y-mediated transcriptional network. ..
- Kabe Y, Yamada J, Uga H, Yamaguchi Y, Wada T, Handa H. NF-Y is essential for the recruitment of RNA polymerase II and inducible transcription of several CCAAT box-containing genes. Mol Cell Biol. 2005;25:512-22 pubmed
- Hu Q, Bhattacharya C, Maity S. CCAAT binding factor (CBF) binding mediates cell cycle activation of topoisomerase IIalpha. Conventional CBF activation domains are not required. J Biol Chem. 2002;277:37191-200 pubmedTo understand the role of the CCAAT binding factor (CBF) in transcription during the cell cycle, we studied the mouse topoisomerase II alpha (topo II alpha) promoter, which is activated during the late S and G(2)/M phases of the cell ..