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Gene Review

grh  -  grainy head

Drosophila melanogaster

Synonyms: BcDNA:LD38807, CG30111, CG42311, CG5058, DNA-binding protein ELF-1, ...
 
 
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Disease relevance of grh

 

High impact information on grh

 

Biological context of grh

 

Anatomical context of grh

  • The expression of Elf-1 during embryogenesis is restricted to nuclei of tissues derived from ectoderm, predominantly the central nervous system (CNS) and the epidermis [9].
  • In the thorax, Grh prolongs neural proliferation by maintaining a mitotically active neuroblast [10].
  • Functional domain studies in Drosophila Schneider cells and endothelial cells revealed examples of positive and negative protein-protein cooperativity involving Sp1, variants of Sp3, Ets-1, Elf-1, and MAZ [11].
  • Here, we show that grh is essential for pNBs to adopt the stem cell programme appropriate to their position within the CNS [12].
  • In contrast, in the context of the IL-2R alpha promoter, conversion of the naturally occurring low affinity Elf-1 site to an optimal site decreased inducible activation of a reporter construct in Jurkat cells [13].
 

Associations of grh with chemical compounds

  • Drosophila tissue-specific transcription factor NTF-1 contains a novel isoleucine-rich activation motif [14].
  • We show that a restricted selectivity for GGAA core-containing sites could be conferred to Ets1 upon changing a single lysine residue within CRIII to the threonine found in Elf1 and E74 at this position [15].
  • Further, we demonstrated that although both Elf-1, an ets family member with significant similarity to the drosophila developmental regulatory protein E74, and Pu.1, a monocyte- and B-cell-specific member of the ets family, bind the purine-rich enhancer region, Elf-1 is the protein which binds predominantly in vivo [16].
 

Physical interactions of grh

  • Moreover, grainyhead interacts genetically with pleiohomeotic in a transgene-based, pairing-dependent silencing assay [17].
  • Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors [18].
  • The CP2-dinG interaction is conserved in evolution with the Drosophila factor grainyhead binding to dring, the fly homologue of dinG [18].
 

Regulatory relationships of grh

  • Purified NTF-1 activates transcription in vitro in a binding site-dependent manner through upstream sequences of the Ubx promoter [8].
  • Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling [19].
  • In the abdomen, Grh terminates neural proliferation by regulating the competence of neuroblasts to undergo apoptosis in response to Abdominal-A expression [10].
 

Other interactions of grh

  • Previous studies have shown that overexpression of NTF-1 in the postblastoderm embryo results in a phenotype that is consistent with a role for this factor in the repression of dpp later in embryogenesis [4].
  • We now demonstrate that the human PcG protein dinG interacts with CP2, a mammalian member of the grainyhead-like family of transcription factors, in vitro and in vivo [18].
  • For example, NTF-1 plays a critical role in the tissue-specific expression of the Drosophila Dopa decarboxylase gene [14].
  • We favour a two-step model for FGF in branching: first, induction of cell movement and apical membrane growth, and second, activation of Grainy head to limit lumen elongation, ensuring that branches reach and attain their characteristic lengths [19].
  • The grainy head transcription factor is essential for the function of the frizzled pathway in the Drosophila wing [20].
 

Analytical, diagnostic and therapeutic context of grh

  • In addition, in situ hybridization experiments revealed that NTF-1 is transcribed in a spatially restricted pattern in the embryo, with the highest level of expression observed in the epidermis and a subset of cells in the CNS [8].

References

  1. Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for Elf-1 and the pets factor. Clark, N.M., Smith, M.J., Hilfinger, J.M., Markovitz, D.M. J. Virol. (1993) [Pubmed]
  2. Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Dynlacht, B.D., Hoey, T., Tjian, R. Cell (1991) [Pubmed]
  3. Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3. Ting, S.B., Wilanowski, T., Auden, A., Hall, M., Voss, A.K., Thomas, T., Parekh, V., Cunningham, J.M., Jane, S.M. Nat. Med. (2003) [Pubmed]
  4. Binding sites for transcription factor NTF-1/Elf-1 contribute to the ventral repression of decapentaplegic. Huang, J.D., Dubnicoff, T., Liaw, G.J., Bai, Y., Valentine, S.A., Shirokawa, J.M., Lengyel, J.A., Courey, A.J. Genes Dev. (1995) [Pubmed]
  5. Drosophila TFIIA directs cooperative DNA binding with TBP and mediates transcriptional activation. Yokomori, K., Zeidler, M.P., Chen, J.L., Verrijzer, C.P., Mlodzik, M., Tjian, R. Genes Dev. (1994) [Pubmed]
  6. Developmental function of Elf-1: an essential transcription factor during embryogenesis in Drosophila. Bray, S.J., Kafatos, F.C. Genes Dev. (1991) [Pubmed]
  7. An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Mace, K.A., Pearson, J.C., McGinnis, W. Science (2005) [Pubmed]
  8. Functional analysis of NTF-1, a developmentally regulated Drosophila transcription factor that binds neuronal cis elements. Dynlacht, B.D., Attardi, L.D., Admon, A., Freeman, M., Tjian, R. Genes Dev. (1989) [Pubmed]
  9. Embryonic expression pattern of a family of Drosophila proteins that interact with a central nervous system regulatory element. Bray, S.J., Burke, B., Brown, N.H., Hirsh, J. Genes Dev. (1989) [Pubmed]
  10. Drosophila Grainyhead specifies late programmes of neural proliferation by regulating the mitotic activity and Hox-dependent apoptosis of neuroblasts. Cenci, C., Gould, A.P. Development (2005) [Pubmed]
  11. Characterization of the human endothelial nitric-oxide synthase promoter. Karantzoulis-Fegaras, F., Antoniou, H., Lai, S.L., Kulkarni, G., D'Abreo, C., Wong, G.K., Miller, T.L., Chan, Y., Atkins, J., Wang, Y., Marsden, P.A. J. Biol. Chem. (1999) [Pubmed]
  12. Regulation of post-embryonic neuroblasts by Drosophila Grainyhead. Almeida, M.S., Bray, S.J. Mech. Dev. (2005) [Pubmed]
  13. Importance of low affinity Elf-1 sites in the regulation of lymphoid-specific inducible gene expression. John, S., Marais, R., Child, R., Light, Y., Leonard, W.J. J. Exp. Med. (1996) [Pubmed]
  14. Drosophila tissue-specific transcription factor NTF-1 contains a novel isoleucine-rich activation motif. Attardi, L.D., Tjian, R. Genes Dev. (1993) [Pubmed]
  15. A single amino-acid substitution in the Ets domain alters core DNA binding specificity of Ets1 to that of the related transcription factors Elf1 and E74. Bosselut, R., Levin, J., Adjadj, E., Ghysdael, J. Nucleic Acids Res. (1993) [Pubmed]
  16. Differential regulation of the human immunodeficiency virus type 2 enhancer in monocytes at various stages of differentiation. Hilfinger, J.M., Clark, N., Smith, M., Robinson, K., Markovitz, D.M. J. Virol. (1993) [Pubmed]
  17. Efficient and specific targeting of Polycomb group proteins requires cooperative interaction between Grainyhead and Pleiohomeotic. Blastyák, A., Mishra, R.K., Karch, F., Gyurkovics, H. Mol. Cell. Biol. (2006) [Pubmed]
  18. Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors. Tuckfield, A., Clouston, D.R., Wilanowski, T.M., Zhao, L.L., Cunningham, J.M., Jane, S.M. Mol. Cell. Biol. (2002) [Pubmed]
  19. Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling. Hemphälä, J., Uv, A., Cantera, R., Bray, S., Samakovlis, C. Development (2003) [Pubmed]
  20. The grainy head transcription factor is essential for the function of the frizzled pathway in the Drosophila wing. Lee, H., Adler, P.N. Mech. Dev. (2004) [Pubmed]
 
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