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Gene Review

YY1  -  YY1 transcription factor

Homo sapiens

Synonyms: DELTA, Delta transcription factor, INO80 complex subunit S, INO80S, NF-E1, ...
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Disease relevance of YY1


Psychiatry related information on YY1

  • A deletion in MDR1 (Delta amino acids 78-97), which alters the substrate stimulation of its ATPase activity, similarly alters the drug dependence of nucleotide trapping [5].
  • Using a cross-sectional survey design, 2,297 adolescents who attended public schools in grades 7 through 12 in one isolated rural Mississippi River Delta county were assessed via a standardized health behavior survey [6].

High impact information on YY1

  • Conversely, YY1 overexpression stimulates p53 ubiquitination and degradation [7].
  • We show that an element within D4Z4 specifically binds a multiprotein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin [8].
  • We propose that, under appropriate conditions, YY1 can function like TBP, as a factor that binds to the core promoter and recruits the polymerase to the initiation complex [9].
  • delta F508 is the most frequent cystic fibrosis (CF) mutation and accounts for approximately 70% of CF chromosomes worldwide [10].
  • TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA [9].

Chemical compound and disease context of YY1


Biological context of YY1

  • Inactivation of endogenous YY1 enhances the accumulation of p53 as well as the expression of p53 target genes in response to DNA damage, and it sensitizes cells to DNA damage-induced apoptosis [16].
  • Hence, our results demonstrate that YY1 regulates the transcriptional activity, acetylation, ubiquitination, and stability of p53 by inhibiting its interaction with the coactivator p300 and by enhancing its interaction with the negative regulator Mdm2 [16].
  • YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [16].
  • Additionally, mutation of the YY1 binding site prevented repression of the promoter by HDAC1 and partially prevented activation of the promoter by trichostatin A [17].
  • Our findings suggest that in the natural context, YY1 activity is regulated through intricate mechanisms involving negative feedback loops, histone deacetylation, and recognition of the cognate DNA sequence affected by acetylation and deacetylation of the YY1 protein [18].

Anatomical context of YY1


Associations of YY1 with chemical compounds

  • Using sucrose gradient centrifugation analysis and immunoprecipitation assays, HCV core was found in a large complex containing B23 and its interacting partner transcription factor YY1 [4].
  • The results with protein pull-down experiments are consistent with the hypothesis that interaction of YY1 with c-Jun is an important mechanism for involucrin repression [19].
  • Association between YY1 and mammalian RPD3 requires a glycine-rich region on YY1 [24].
  • We found that glucose strongly stimulates O-linked N-acetylglucosaminylation (O-GlcNAcylation) on YY1 [25].
  • YAF2 appears to have a promyogenic regulatory role, since overexpression of YAF2 in C2 myoblasts stimulates myogenic promoter activity normally restricted by YY1 [26].
  • These data indicate that PGF2alpha enhances a direct YY1/StAR promoter interaction and the recruitment of HDAC1 to the promoter, thereby preventing transcriptional activation of the StAR gene [27].

Physical interactions of YY1

  • Furthermore, FKBP25 can alter the DNA-binding activity of YY1 [28].
  • Here, we demonstrate that the transcription factor Yin Yang 1 (YY1) interacts with p53 and inhibits its transcriptional activity [16].
  • The finding that the YY1-binding allele causes a significant increase in CFTR expression in vitro may allow a better understanding of the milder phenotype observed in patients who carry a severe CF mutation within the same gene [29].
  • By using yeast three-hybrid assay, we demonstrated that hGABP beta and YY1 formed a complex only in the presence of YEAF1, indicating that YEAF1 is a bridging factor of these two transcription factors [30].
  • Individuals bearing haplotypic variants of the MCP-4 core promoter that avidly bind the transcription factor YY-1 had higher plasma levels of MCP-4 than did individuals with variants with lower binding avidity (490, 360, and 360 pg/ml; P < 0.01) [31].

Enzymatic interactions of YY1

  • Nuclear cathepsin B-like protease cleaves transcription factor YY1 in differentiated cells [32].
  • The best substrates for CPB2.8 Delta CTE were also well hydrolysed by cathepsin L, however, the best inhibitors of the parasite enzyme have low affinity to cathepsin L. These promising data provide leads for the design of anti-parasitic drugs directed against the leishmanial enzyme [33].

Co-localisations of YY1

  • Co-immunoprecipitation and immunostaining of cells further indicated that YY1AP co-localizes with YY1 in the nucleus [34].
  • PIASy colocalizes with YY1 in the nucleus, stabilizes YY1 in vivo, and differentially regulates YY1 transcriptional activity on different target promoters [35].

Regulatory relationships of YY1

  • Consequently, YY1 enhances Mdm2-mediated ubiquitination of p53 [16].
  • Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs [18].
  • YY1 transcription factor down-regulates expression of CCR5, a major coreceptor for HIV-1 [1].
  • Increasing doses of a YY-1 expression vector induced significantly greater reporter activity from MCP-4 core promoter expression constructs of the wild-type compared with the variant sequence in transient transfection experiments [31].
  • Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter [36].

Other interactions of YY1


Analytical, diagnostic and therapeutic context of YY1


  1. YY1 transcription factor down-regulates expression of CCR5, a major coreceptor for HIV-1. Moriuchi, M., Moriuchi, H. J. Biol. Chem. (2003) [Pubmed]
  2. Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells. Begon, D.Y., Delacroix, L., Vernimmen, D., Jackers, P., Winkler, R. J. Biol. Chem. (2005) [Pubmed]
  3. Cloning, chromosomal localization and promoter analysis of the human transcription factor YY1. Yao, Y.L., Dupont, B.R., Ghosh, S., Fang, Y., Leach, R.J., Seto, E. Nucleic Acids Res. (1998) [Pubmed]
  4. Hepatitis C virus core protein recruits nucleolar phosphoprotein B23 and coactivator p300 to relieve the repression effect of transcriptional factor YY1 on B23 gene expression. Mai, R.T., Yeh, T.S., Kao, C.F., Sun, S.K., Huang, H.H., Wu Lee, Y.H. Oncogene (2006) [Pubmed]
  5. Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. Cooperation of the nucleotide binding domains. Szabó, K., Welker, E., Bakos, n.u.l.l., Müller, M., Roninson, I., Váradi, A., Sarkadi, B. J. Biol. Chem. (1998) [Pubmed]
  6. The effects of mental health factors on ambulatory care visits by rural teens. Rickert, V.I., Pope, S.K., Tilford, J.M., Wayne, J., Scholle, S.H., Kelleher, K.J. The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association. (1996) [Pubmed]
  7. Yin Yang 1 is a negative regulator of p53. Sui, G., Affar, e.l. .B., Shi, Y., Brignone, C., Wall, N.R., Yin, P., Donohoe, M., Luke, M.P., Calvo, D., Grossman, S.R., Shi, Y. Cell (2004) [Pubmed]
  8. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Gabellini, D., Green, M.R., Tupler, R. Cell (2002) [Pubmed]
  9. TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA. Usheva, A., Shenk, T. Cell (1994) [Pubmed]
  10. The origin of the major cystic fibrosis mutation (delta F508) in European populations. Morral, N., Bertranpetit, J., Estivill, X., Nunes, V., Casals, T., Giménez, J., Reis, A., Varon-Mateeva, R., Macek, M., Kalaydjieva, L. Nat. Genet. (1994) [Pubmed]
  11. Maintenance of integrated proviral gene expression requires Brm, a catalytic subunit of SWI/SNF complex. Mizutani, T., Ito, T., Nishina, M., Yamamichi, N., Watanabe, A., Iba, H. J. Biol. Chem. (2002) [Pubmed]
  12. Chloride conductance and genetic background modulate the cystic fibrosis phenotype of Delta F508 homozygous twins and siblings. Bronsveld, I., Mekus, F., Bijman, J., Ballmann, M., de Jonge, H.R., Laabs, U., Halley, D.J., Ellemunter, H., Mastella, G., Thomas, S., Veeze, H.J., Tümmler, B. J. Clin. Invest. (2001) [Pubmed]
  13. Organic solutes rescue the functional defect in delta F508 cystic fibrosis transmembrane conductance regulator. Zhang, X.M., Wang, X.T., Yue, H., Leung, S.W., Thibodeau, P.H., Thomas, P.J., Guggino, S.E. J. Biol. Chem. (2003) [Pubmed]
  14. The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin. Glas, J., Török, H.P., Simperl, C., König, A., Martin, K., Schmidt, F., Schaefer, M., Schiemann, U., Folwaczny, C. Clin. Immunol. (2003) [Pubmed]
  15. Role of lipooligosaccharide in Opa-independent invasion of Neisseria gonorrhoeae into human epithelial cells. Song, W., Ma, L., Chen, R., Stein, D.C. J. Exp. Med. (2000) [Pubmed]
  16. YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress. Grönroos, E., Terentiev, A.A., Punga, T., Ericsson, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. Histone deacetylase activity represses gamma interferon-inducible HLA-DR gene expression following the establishment of a DNase I-hypersensitive chromatin conformation. Osborne, A., Zhang, H., Yang, W.M., Seto, E., Blanck, G. Mol. Cell. Biol. (2001) [Pubmed]
  18. Regulation of transcription factor YY1 by acetylation and deacetylation. Yao, Y.L., Yang, W.M., Seto, E. Mol. Cell. Biol. (2001) [Pubmed]
  19. YY-1 and c-Jun transcription factors participate in the repression of the human involucrin promoter. Alvarez-Salas, L.M., Benitez-Hess, M.L., Dipaolo, J.A. Int. J. Oncol. (2005) [Pubmed]
  20. Expression of Polycomb-group genes in human ovarian follicles, oocytes and preimplantation embryos. Hinkins, M., Huntriss, J., Miller, D., Picton, H.M. Reproduction (2005) [Pubmed]
  21. ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1. Li, M., Baumeister, P., Roy, B., Phan, T., Foti, D., Luo, S., Lee, A.S. Mol. Cell. Biol. (2000) [Pubmed]
  22. Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element. Becker, K.G., Swergold, G.D., Ozato, K., Thayer, R.E. Hum. Mol. Genet. (1993) [Pubmed]
  23. Association of transcription factor YY1 with the high molecular weight Notch complex suppresses the transactivation activity of Notch. Yeh, T.S., Lin, Y.M., Hsieh, R.H., Tseng, M.J. J. Biol. Chem. (2003) [Pubmed]
  24. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Yang, W.M., Inouye, C., Zeng, Y., Bearss, D., Seto, E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. YY1 is regulated by O-linked N-acetylglucosaminylation (O-glcNAcylation). Hiromura, M., Choi, C.H., Sabourin, N.A., Jones, H., Bachvarov, D., Usheva, A. J. Biol. Chem. (2003) [Pubmed]
  26. Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1. Kalenik, J.L., Chen, D., Bradley, M.E., Chen, S.J., Lee, T.C. Nucleic Acids Res. (1997) [Pubmed]
  27. Prostaglandin F2alpha suppresses rat steroidogenic acute regulatory protein expression via induction of Yin Yang 1 protein and recruitment of histone deacetylase 1 protein. Liu, Q., Merkler, K.A., Zhang, X., McLean, M.P. Endocrinology (2007) [Pubmed]
  28. The FK506-binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1. Yang, W.M., Yao, Y.L., Seto, E. EMBO J. (2001) [Pubmed]
  29. A naturally occurring sequence variation that creates a YY1 element is associated with increased cystic fibrosis transmembrane conductance regulator gene expression. Romey, M.C., Pallares-Ruiz, N., Mange, A., Mettling, C., Peytavi, R., Demaille, J., Claustres, M. J. Biol. Chem. (2000) [Pubmed]
  30. YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors. Sawa, C., Yoshikawa, T., Matsuda-Suzuki, F., Deléhouzée, S., Goto, M., Watanabe, H., Sawada, J., Kataoka, K., Handa, H. J. Biol. Chem. (2002) [Pubmed]
  31. Monocyte chemoattractant protein-4 core promoter genetic variants: influence on YY-1 affinity and plasma levels. Kalayci, O., Birben, E., Wu, L., Oguma, T., Storm Van's Gravesande, K., Subramaniam, V., Sheldon, H.K., Silverman, E.S., Lilly, C.M. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  32. Nuclear cathepsin B-like protease cleaves transcription factor YY1 in differentiated cells. Pizzorno, M.C. Biochim. Biophys. Acta (2001) [Pubmed]
  33. Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania mexicana. Alves, L.C., Judice, W.A., St Hilaire, P.M., Meldal, M., Sanderson, S.J., Mottram, J.C., Coombs, G.H., Juliano, L., Juliano, M.A. Mol. Biochem. Parasitol. (2001) [Pubmed]
  34. YY1AP, a novel co-activator of YY1. Wang, C.Y., Liang, Y.J., Lin, Y.S., Shih, H.M., Jou, Y.S., Yu, W.C. J. Biol. Chem. (2004) [Pubmed]
  35. PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger. Deng, Z., Wan, M., Sui, G. Mol. Cell. Biol. (2007) [Pubmed]
  36. Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites. Joshi, B., Rastogi, S., Morris, M., Carastro, L.M., DeCook, C., Seto, E., Chellappan, S.P. Biochem. J. (2007) [Pubmed]
  37. Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function. Schlisio, S., Halperin, T., Vidal, M., Nevins, J.R. EMBO J. (2002) [Pubmed]
  38. Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. He, G., Margolis, D.M. Mol. Cell. Biol. (2002) [Pubmed]
  39. YY1 binding within the human HSD3B2 gene intron 1 is required for maximal basal promoter activity: identification of YY1 as the 3beta1-A factor. Foti, D.M., Reichardt, J.K. J. Mol. Endocrinol. (2004) [Pubmed]
  40. The transcriptional factor YY1 upregulates the novel invasion suppressor HLJ1 expression and inhibits cancer cell invasion. Wang, C.C., Tsai, M.F., Hong, T.M., Chang, G.C., Chen, C.Y., Yang, W.M., Chen, J.J., Yang, P.C. Oncogene (2005) [Pubmed]
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