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Gene Review

Cited2  -  Cbp/p300-interacting transactivator, with...

Mus musculus

Synonyms: AI835299, Cbp/p300-interacting transactivator 2, ER154-like, MRG-1, MSG-related protein 1, ...
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Disease relevance of Cited2

  • Morphological and Doppler echocardiographic analyses of Cited2(-/-) embryos reveal severe cardiovascular abnormalities, including pulmonic arterial stenosis and ventricular septal defects accompanied by high peak outflow velocities, features of the human congenital cardiac defect termed tetralogy of Fallot [1].
  • The hypoxia of the outflow tract and interventricular septum peaked at E13.5 and dissipated by E15.5 in wild-type hearts, but persisted in E15.5 Cited2(-/-) hearts [2].
  • In this study, we confirmed that both mRNA and protein levels of Cited2 are down-regulated in MDA-MB-231 breast cancer cells [3].

High impact information on Cited2

  • Malformations of the septum, outflow tract and aortic arch are the most common congenital cardiovascular defects and occur in mice lacking Cited2, a transcriptional coactivator of TFAP2 [4].
  • We have used this procedure to describe the cardiac phenotype and associated blood vessels of trisomic 16 (Ts16) and Cited2-null mutant mice, as well as the expression pattern of an Myf5 enhancer/beta-galactosidase transgene [5].
  • As certain Tfap2 isoforms are essential in neural crest, neural tube and cardiac development, we propose that abnormal embryogenesis in mice lacking Cited2 results, at least in part, from its role as a Tfap2 co-activator [6].
  • Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator [6].
  • Here we show that Cited2-/- embryos die with cardiac malformations, adrenal agenesis, abnormal cranial ganglia and exencephaly [6].

Chemical compound and disease context of Cited2


Biological context of Cited2

  • Although abnormal left-right patterning has a major impact on the cardiac phenotype in Cited2-null embryos, laterality defects are only observed in a proportion of these embryos [8].
  • The transcriptional modulator Cited2 is essential for embryonic development: Cited2-null embryos die during gestation with profound developmental abnormalities, including cardiac malformations, exencephaly and adrenal agenesis [8].
  • Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development [8].
  • In particular, muscular ventricular septal defects and reduced cell density in the atrioventricular (AV) endocardial cushions are evident in Cited2-null embryos [8].
  • Given that Cited2 is expressed in both trophoblasts and the fetal vasculature, the observed defects fit well with the sites of gene expression [9].

Anatomical context of Cited2


Associations of Cited2 with chemical compounds


Regulatory relationships of Cited2


Other interactions of Cited2

  • We found that Cited2(-/-) fibroblasts had reduced expression of the polycomb-group genes Bmi1 and Mel18, which function as INK4a/ARF and Hox repressors [10].
  • Transfection of mrg1 cDNA into TS1, an IL-9-dependent mouse T cell line, converted these cells to IL-9-independent growth through a nonautocrine mechanism [13].
  • MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity [13].
  • In genetic NTD models such as Cart1, splotch, Cited2, and crooked tail, and NTD induced by teratogens including valproic acid and fumonisins, the incidence of defects is reduced by maternal folic acid supplementation [14].
  • Deletion of Hif1a (which encodes HIF-1alpha) in Cited2(-/-) lens specifically eliminated the excessive accumulation of cellular mass and aberrant vasculature in the developing vitreous without affecting the corneal-lenticular stalk phenotype [15].

Analytical, diagnostic and therapeutic context of Cited2


  1. The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation. Yin, Z., Haynie, J., Yang, X., Han, B., Kiatchoosakun, S., Restivo, J., Yuan, S., Prabhakar, N.R., Herrup, K., Conlon, R.A., Hoit, B.D., Watanabe, M., Yang, Y.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Partial rescue of defects in Cited2-deficient embryos by HIF-1alpha heterozygosity. Xu, B., Doughman, Y., Turakhia, M., Jiang, W., Landsettle, C.E., Agani, F.H., Semenza, G.L., Watanabe, M., Yang, Y.C. Dev. Biol. (2007) [Pubmed]
  3. Post-transcriptional control of Cited2 by transforming growth factor beta. Regulation via Smads and Cited2 coding region. Chou, Y.T., Yang, Y.C. J. Biol. Chem. (2006) [Pubmed]
  4. Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Bamforth, S.D., Bragança, J., Farthing, C.R., Schneider, J.E., Broadbent, C., Michell, A.C., Clarke, K., Neubauer, S., Norris, D., Brown, N.A., Anderson, R.H., Bhattacharya, S. Nat. Genet. (2004) [Pubmed]
  5. Phenotyping transgenic embryos: a rapid 3-D screening method based on episcopic fluorescence image capturing. Weninger, W.J., Mohun, T. Nat. Genet. (2002) [Pubmed]
  6. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Bamforth, S.D., Bragança, J., Eloranta, J.J., Murdoch, J.N., Marques, F.I., Kranc, K.R., Farza, H., Henderson, D.J., Hurst, H.C., Bhattacharya, S. Nat. Genet. (2001) [Pubmed]
  7. Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Bhattacharya, S., Michels, C.L., Leung, M.K., Arany, Z.P., Kung, A.L., Livingston, D.M. Genes Dev. (1999) [Pubmed]
  8. Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development. Weninger, W.J., Floro, K.L., Bennett, M.B., Withington, S.L., Preis, J.I., Barbera, J.P., Mohun, T.J., Dunwoodie, S.L. Development (2005) [Pubmed]
  9. Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta. Withington, S.L., Scott, A.N., Saunders, D.N., Lopes Floro, K., Preis, J.I., Michalicek, J., Maclean, K., Sparrow, D.B., Barbera, J.P., Dunwoodie, S.L. Dev. Biol. (2006) [Pubmed]
  10. Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Kranc, K.R., Bamforth, S.D., Bragança, J., Norbury, C., van Lohuizen, M., Bhattacharya, S. Mol. Cell. Biol. (2003) [Pubmed]
  11. Folic acid prevents exencephaly in Cited2 deficient mice. Barbera, J.P., Rodriguez, T.A., Greene, N.D., Weninger, W.J., Simeone, A., Copp, A.J., Beddington, R.S., Dunwoodie, S. Hum. Mol. Genet. (2002) [Pubmed]
  12. Cited2 modulates TGF-beta-mediated upregulation of MMP9. Chou, Y.T., Wang, H., Chen, Y., Danielpour, D., Yang, Y.C. Oncogene (2006) [Pubmed]
  13. MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Sun, H.B., Zhu, Y.X., Yin, T., Sledge, G., Yang, Y.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  14. Mouse models of neural tube defects: investigating preventive mechanisms. Greene, N.D., Copp, A.J. American journal of medical genetics. Part C, Seminars in medical genetics. (2005) [Pubmed]
  15. Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Chen, Y., Doughman, Y.Q., Gu, S., Jarrell, A., Aota, S., Cvekl, A., Watanabe, M., Dunwoodie, S.L., Johnson, R.S., van Heyningen, V., Kleinjan, D.A., Beebe, D.C., Yang, Y.C. Development (2008) [Pubmed]
  16. Expression analysis of the chicken homologue of CITED2 during early stages of embryonic development. Schlange, T., Andrée, B., Arnold, H., Brand, T. Mech. Dev. (2000) [Pubmed]
  17. DNA microarray analysis of cannabinoid signaling in mouse brain in vivo. Parmentier-Batteur, S., Jin, K., Xie, L., Mao, X.O., Greenberg, D.A. Mol. Pharmacol. (2002) [Pubmed]
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