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Gene Review

h  -  hairy

Drosophila melanogaster

Synonyms: 8247, CG6494, Dmel\CG6494, HRY, Hairy, ...
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High impact information on h

  • Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination [1].
  • Groucho acts as a corepressor for a subset of negative regulators, including Hairy and Engrailed [2].
  • Previously, Gro was proposed to mediate repression by the Hairy-related family of basic helix-loop-helix proteins [2].
  • hairy (h) acts as a negative regulator in both embryonic segmentation and adult peripheral nervous system (PNS) development in Drosophila [3].
  • HES6 is a novel member of the family of basic helix-loop-helix mammalian homologues of Drosophila Hairy and Enhancer of split [4].

Biological context of h

  • Notch acted in part through downregulation of Hairy; Hh signaling downregulated Hairy independently of Notch [5].
  • This amino acid sequence has recently been demonstrated in the mammalian protein C-terminal interacting protein (CtIP) and a number of Drosophila repressors including Snail, Knirps and Hairy [6].
  • To explore the ability of these proteins to function as promoter-bound regulators in vivo, we examined the effects of Hairy and Runt derivatives containing heterologous transcriptional activation domains (HairyAct and RunAct) [7].
  • Members of the Hairy/Enhancer of Split family of basic helix-loop-helix (bHLH) transcription factors are regulated by the Notch signaling pathway in vertebrate and Drosophila embryos and control cell fates and establishment of sharp boundaries of gene expression [8].
  • hairy: A quantitative trait locus for drosophila sensory bristle number [9].

Anatomical context of h

  • Activation of Raf is both necessary and sufficient to cause pre-proneural cells to become proneural, a transition marked by downregulation of Hairy and upregulation of the proneural activator, Atonal (Ato), which initiates differentiation of the R8 photoreceptor [10].
  • The unique and complementary expression patterns of this novel subfamily of bHLH proteins suggest a previously unrecognized role for Hairy-related pathways in segmental patterning of the heart and pharyngeal arches, among other organs [8].
  • DEC1 is a basic helix-loop-helix (bHLH) protein related to Drosophila Hairy, Enhancer of split and HES, and involved in the control of proliferation and/or differentiation of chondrocytes, neurons, etc [11].
  • Overexpression of a Ci-Su(H) fusion protein containing the Drosophila Hairy repression domain interferes with notochord differentiation, producing mutant tadpoles with shortened tails [12].

Associations of h with chemical compounds

  • However, the motifs in Knirps and Hairy did not adopt well-defined structures in TFE/water mixtures as shown by the absence of medium range NOEs and a high proportion of signal overlap [6].
  • While hairy/E(spl) proteins are characterized by an invariant proline residue in the basic domain and a carboxyterminal groucho-binding WRPW motif, our genes encode a carboxyterminal KPYRPWG sequence and were thus designated as Hey genes (Hairy/E(spl)-related with YRPW motif) [13].

Physical interactions of h

  • While Hairy is probably not the only segmentation gene interacting with dCtBP, we show dose-sensitive genetic interactions between dCtBP and hairy mutations [14].
  • The Groucho protein interacts with Hairy-related transcription factors to regulate segmentation, neurogenesis and sex determination [15].
  • Our results strongly suggest that Hairy normally acts as a promoter-bound repressor of fushi tarazu, runt and odd-skipped, and that Runt directly represses even-skipped [7].

Other interactions of h

  • We show that Hairy and Dl function concertedly and nonredundantly to define periodic ac expression [16].
  • Drosophila CtBP: a Hairy-interacting protein required for embryonic segmentation and hairy-mediated transcriptional repression [14].
  • Using an in vivo repression assay, we identify a functional repressor domain in Huckebein that contains an FRPW tetrapeptide, similar to the WRPW Groucho-recruitment domain found in Hairy-related repressor proteins [17].
  • The ac/sc expression domains are delimited by the Hairy repressor, which is itself periodically expressed [18].
  • The first signal, Decapentaplegic (Dpp), acts at long range on undifferentiated cells anterior to the furrow, causing them to enter a 'pre-proneural' state marked by upregulated expression of the transcription factor Hairy [10].


  1. Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination. Rosenberg, M.I., Parkhurst, S.M. Cell (2002) [Pubmed]
  2. Groucho acts as a corepressor for a subset of negative regulators, including Hairy and Engrailed. Jiménez, G., Paroush, Z., Ish-Horowicz, D. Genes Dev. (1997) [Pubmed]
  3. Negative regulation of proneural gene activity: hairy is a direct transcriptional repressor of achaete. Van Doren, M., Bailey, A.M., Esnayra, J., Ede, K., Posakony, J.W. Genes Dev. (1994) [Pubmed]
  4. HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. Gao, X., Chandra, T., Gratton, M.O., Quélo, I., Prud'homme, J., Stifani, S., St-Arnaud, R. J. Cell Biol. (2001) [Pubmed]
  5. Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development. Fu, W., Baker, N.E. Development (2003) [Pubmed]
  6. Structural determinants outside the PXDLS sequence affect the interaction of adenovirus E1A, C-terminal interacting protein and Drosophila repressors with C-terminal binding protein. Molloy, D.P., Barral, P.M., Bremner, K.H., Gallimore, P.H., Grand, R.J. Biochim. Biophys. Acta (2001) [Pubmed]
  7. In vivo interactions of the Drosophila Hairy and Runt transcriptional repressors with target promoters. Jiménez, G., Pinchin, S.M., Ish-Horowicz, D. EMBO J. (1996) [Pubmed]
  8. HRT1, HRT2, and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic, and pharyngeal arch segments. Nakagawa, O., Nakagawa, M., Richardson, J.A., Olson, E.N., Srivastava, D. Dev. Biol. (1999) [Pubmed]
  9. hairy: A quantitative trait locus for drosophila sensory bristle number. Robin, C., Lyman, R.F., Long, A.D., Langley, C.H., Mackay, T.F. Genetics (2002) [Pubmed]
  10. Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. Greenwood, S., Struhl, G. Development (1999) [Pubmed]
  11. Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins. Fujimoto, K., Shen, M., Noshiro, M., Matsubara, K., Shingu, S., Honda, K., Yoshida, E., Suardita, K., Matsuda, Y., Kato, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. Suppressor of hairless activates brachyury expression in the Ciona embryo. Corbo, J.C., Fujiwara, S., Levine, M., Di Gregorio, A. Dev. Biol. (1998) [Pubmed]
  13. Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Leimeister, C., Externbrink, A., Klamt, B., Gessler, M. Mech. Dev. (1999) [Pubmed]
  14. Drosophila CtBP: a Hairy-interacting protein required for embryonic segmentation and hairy-mediated transcriptional repression. Poortinga, G., Watanabe, M., Parkhurst, S.M. EMBO J. (1998) [Pubmed]
  15. Transcripts of Grg4, a murine groucho-related gene, are detected in adjacent tissues to other murine neurogenic gene homologues during embryonic development. Koop, K.E., MacDonald, L.M., Lobe, C.G. Mech. Dev. (1996) [Pubmed]
  16. Delta and Hairy establish a periodic prepattern that positions sensory bristles in Drosophila legs. Joshi, M., Buchanan, K.T., Shroff, S., Orenic, T.V. Dev. Biol. (2006) [Pubmed]
  17. Huckebein repressor activity in Drosophila terminal patterning is mediated by Groucho. Goldstein, R.E., Jiménez, G., Cook, O., Gur, D., Paroush, Z. Development (1999) [Pubmed]
  18. Opposing inputs by Hedgehog and Brinker define a stripe of hairy expression in the Drosophila leg imaginal disc. Kwon, C., Hays, R., Fetting, J., Orenic, T.V. Development (2004) [Pubmed]
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