Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.

Bailey, Adina; Posakony, James W.

doi:10.1101/gad.9.21.2609

Cited by 555 publications

(529 citation statements)

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“…[8][9][10][11] DNA sequences similar to the consensus have been identified within the promoter regions of Notch target genes in organisms ranging from flies and worms to humans and even in the genomes of the herpesviruses, Epstein-Barr virus and Kaposi's sarcomaassociated herpesvirus. [12][13][14][15] However, more complicated arrangements of CSL binding sites have also been observed, for example the enhancer of split gene complex (E(spl)-C) in flies. 12 Certain genes of the E(spl)-C contain a unique promoter architecture, termed Su(H)-paired site (SPS), consisting of two CSL binding sites arranged in a head-to-head manner with an approximately 16 base pair A/T rich spacer sequence [ Fig.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15] However, more complicated arrangements of CSL binding sites have also been observed, for example the enhancer of split gene complex (E(spl)-C) in flies. 12 Certain genes of the E(spl)-C contain a unique promoter architecture, termed Su(H)-paired site (SPS), consisting of two CSL binding sites arranged in a head-to-head manner with an approximately 16 base pair A/T rich spacer sequence [ Fig. 1(A)].…”

Section: Introductionmentioning

confidence: 99%

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Thermodynamic and structural insights into CSL‐DNA complexes

Friedmann

Kovall

2009

Protein Science

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The Notch pathway is an intercellular signaling mechanism that plays important roles in cell fates decisions throughout the developing and adult organism. Extracellular complexation of Notch receptors with ligands ultimately results in changes in gene expression, which is regulated by the nuclear effector of the pathway, CSL (C-promoter binding factor 1 (CBF-1), suppressor of hairless (Su(H)), lin-12 and glp-1 (Lag-1)). CSL is a DNA binding protein that is involved in both repression and activation of transcription from genes that are responsive to Notch signaling. One well-characterized Notch target gene is hairy and enhancer of split-1 (HES-1), which is regulated by a promoter element consisting of two CSL binding sites oriented in a head-to-head arrangement. Although previous studies have identified in vivo and consensus binding sites for CSL, and crystal structures of these complexes have been determined, to date, a quantitative description of the energetics that underlie CSL-DNA binding is unknown. Here, we provide a thermodynamic and structural analysis of the interaction between CSL and the two individual sites that comprise the HES-1 promoter element. Our comprehensive studies that analyze binding as a function of temperature, salt, and pH reveal moderate, but distinct, differences in the affinities of CSL for the two HES-1 binding sites. Similarly, our structural results indicate that overall CSL binds both DNA sites in a similar manner; however, minor changes are observed in both the conformation of CSL and DNA. Taken together, our results provide a quantitative and biophysical basis for understanding how CSL interacts with DNA sites in vivo.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermodynamic and structural insights into CSL‐DNA complexes

Friedmann

Kovall

2009

Protein Science

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“…During Drosophila sense organ development, activation of the Notch receptor in response to binding of the ligand Delta induces transcription of genes of the Enhancer of Split complex [E(spl)] (Jennings et al 1994). The Drosophila Suppressor of Hairless [Su(H)] protein binds to the promoter regions of the E(Spl) genes and is a key component in Notch-mediated activation (Bailey and Posakony 1995;Lecourtois and Schweisguth 1995). Activation of Su(H) is thought to be dependent on a direct physical interaction with the Notch cytoplasmic domain.…”

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confidence: 99%

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Kao¹,

Ordentlich²,

et al. 1998

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“…Hairy and Enhancer of split [E(spl)] (HES) family members can be directly activated by the transcription factor Su(H) (Bailey and Posakony, 1995;Lecourtois and Schweisguth, 1995;Jarriault et al, 1998). Hes proteins interact with the corepressor Groucho by means of a C-terminal tetrapeptide and directly repress the expression of achaete-scute homologues (ASH; Paroush et al, 1994;Fisher et al, 1996;Grbavec and Stifani, 1996;Jimenez et al, 1997;Fisher and Caudy, 1998;Chen and Courey, 2000).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of Xenopus Hey‐1: A downstream mediator of Notch signaling

Rones

Woda

Mercola

et al. 2002

Developmental Dynamics

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Regulation of Notch signaling likely occurs, at least in part, at the level of basic helix-loop-helix (bHLH) transcription factors that function downstream of Suppressor of Hairless (Su(H)) in the Notch pathway. To begin to characterize modulation of Notch signaling during organogenesis, we examined the bHLH transcription factor, XHey-1 (hairy related-1) in early Xenopus laevis embryos. XHey-1 is expressed in numerous tissues during early development including the somites, head, embryonic kidneys, and heart. Importantly, the expression of XHey-1 was significantly altered in response to perturbation of Notch signaling by means of inducible constructs that served to either activate or suppress Notch signaling through Su(H) in a temporally controlled manner.

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Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.

Cited by 555 publications

References 59 publications

Thermodynamic and structural insights into CSL‐DNA complexes

Thermodynamic and structural insights into CSL‐DNA complexes

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Isolation and characterization of Xenopus Hey‐1: A downstream mediator of Notch signaling

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