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].

References