Competition for Overlapping Sites in the Regulatory Region of the
            <i>Drosophila</i>
            Gene
            <i>Krüppel</i>

Hoch, Michael; Gerwin, Nicole; Taubert, Heike; Jäckle, Herbert

doi:10.1126/science.1348871

Cited by 133 publications

(110 citation statements)

References 63 publications

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“…Nevertheless, PNR shares a TLX peculiarity, the substitution of the otherwise universally conserved lysine residue by a serine, which in TLX, seems to allow preferential recognition of the AAGTCA site (5,17,25). This combination of features presented us with the opportunity to examine the effect of individual P box residues.…”

Section: Discussionmentioning

confidence: 99%

Identification of a photoreceptor cell-specific nuclear receptor

Kobayashi

Takezawa

Hara

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

183

177

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Nuclear receptors comprise a large and expanding family of transcription factors involved in diverse aspects of animal physiology and development, the functions of which can be modulated in a spatial and temporal manner by access to small lipophilic ligands and/or the specificity of their own localized expression. Here we report the identification of a human nuclear receptor that reveals a unique proximal box (CNGCSG) in the DNA-binding domain. The conservation of this feature in its nematode counterpart suggests the requirement for this type of P box in the genetic cascades mediated by nuclear receptors in a wide variety of animal species. The expression of this receptor, PNR (photoreceptor-specific nuclear receptor), appears strongly restricted in the retina, exclusively in photoreceptor cells. In human cell lines, PNR expression was observed in Y79 retinoblastoma along with other photoreceptor marker genes such as CRX. Among vertebrate receptors, PNR shares structural kinship with an orphan receptor TLX, and despite distinct differences in the DNA binding domain, PNR is able to recognize a subset of TLX target sequences in vitro. Analyses of the human PNR gene revealed its chromosomal position as 15q24, a site that has recently been reported as a susceptible region for retinal degeneration. These data support a role for PNR in the regulation of signalling pathways intrinsic to the photoreceptor cell function.

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Section: Discussionmentioning

confidence: 99%

Identification of a photoreceptor cell-specific nuclear receptor

Kobayashi

Takezawa

Hara

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

183

177

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“…A similar inference applies to another target gene of tll, namely Krüppel (Kr). tll acts as a repressor of Kr in Drosophila (33,34). In Tribolium, Tc-Kr expression occurs at the posterior pole of the blastoderm embryo (35), overlapping with the early Tc-tll expression.…”

Section: Discussionmentioning

confidence: 99%

Conserved and divergent aspects of terminal patterning in the beetle Tribolium castaneum

Schröder

Eckert

Wolff

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

113

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To infer similarities and differences in terminal pattern formation in insects, we analyzed several of the key genes of this process in the beetle Tribolium castaneum. We cloned two genes of the terminal pattern cascade, namely tailless (tll) and forkhead ( fkh), from Tribolium and studied their expression patterns. In addition, we analyzed the pattern of MAP kinase activation at blastoderm stage as a possible signature for torso-dependent signaling. Further, we analyzed the late expression of the previously cloned Tribolium caudal (Tc-cad) gene. Finally, we used the upstream region of Tc-tll to drive a reporter gene construct in Drosophila. We find that this construct is activated at the terminal regions in Drosophila, suggesting that the torso-dependent pathway is conserved between the species. We show that most of the expression patterns of the genes studied here are similar in Drosophila and Tribolium, suggesting conserved functions. There is, however, one exception, namely the early function of Tc-tll at the posterior pole. In Drosophila, the posterior tll expression is involved in the direct regulation of the target genes of the terminal pathway. In Tribolium, posterior Tc-tll expression occurs only for a short time and ceases before the target genes known from Drosophila are activated. Thus, we infer that Tc-tll does not function as a direct regulator of segmentation genes at the posterior end. It is more likely to be involved in the early specification of a group of ''terminal'' cells, which begin to differentiate only at a later stage of embryogenesis, when much of the abdominal segmentation process is complete. Thus, there appears to have been a major shift in tll function during the evolutionary transition from short germ to long germ embryogenesis.tailless ͉ forkhead ͉ caudal ͉ torso ͉ short germ insect T erminal pattern formation in Drosophila is maternally initiated at both poles of the egg through the torso-mediated receptor tyrosine kinase pathway (1). Two zygotic gap genes, namely tailless (tll) and huckebein (hkb), are activated in a concentration-dependent manner in response to the signaling activity of torso (tor) (2, 3). Both tll and hkb code for transcription factors that regulate further target genes, among them forkhead ( fkh), brachyenteron (byn), and the terminal hunchback (hb) and wingless (wg) domains (4-8). fkh and wg are also activated by caudal (cad) (8), which is expressed maternally as well as zygotically in the posterior half of the embryo (9, 10). Together these genes are required for patterning the terminal cuticle structures, such as the most posterior segments, the anal pads, and the telson, as well as the stomodaeum, the hindgut, and the Malpighian tubules.Embryogenesis in the flour beetle Tribolium represents a more ancestral form of embryogenesis in insects (11). Nevertheless, it was possible to clone most of the early segmentation genes known from Drosophila also from Tribolium, and the analysis of their expression patterns has suggested that they may have similar functi...

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“…CtBP-independent activity can in some cases be directly attributed to direct competition with activator for DNA binding (Hoch et al, 1992;Nibu et al, 2003); however, the CtBPindependent activity of Knirps can repress activators on elements where sites are not overlapping (Keller et al, 2000;Ryu and Arnosti, 2003), and overexpression of the DNAbinding domain of Knirps (Knirps1-105) is insufficient to mediate repression of endogenous eve enhancers (data not shown). Cell culture and transgenic embryo assays indicate that both CtBP-dependent and independent repression activities of Knirps have very similar characteristics with respect to activator specificity, distance dependence and overall potency, thus the targets and molecular mechanisms might well be similar in each case (Ryu and Arnosti, 2003;Sutrias-Grau and Arnosti, 2004).…”

Section: Repression Mechanismsmentioning

confidence: 99%

Quantitative contributions of CtBP-dependent and -independent repression activities of Knirps

et al. 2004

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The Drosophila Knirps protein is a short-range transcriptional repressor that locally inhibits activators by recruiting the CtBP co-repressor. Knirps also possesses CtBP-independent repression activity. The functional importance of multiple repression activities is not well understood, but the finding that Knirps does not repress some cis-regulatory elements in the absence of CtBP suggested that the co-factor may supply a unique function essential to repress certain types of activators. We assayed CtBP-dependent and -independent repression domains of Knirps in Drosophila embryos, and found that the CtBPindependent activity, when provided at higher than normal levels, can repress an eve regulatory element that normally requires CtBP. Dose response analysis revealed that the activity of Knirps containing both CtBP-dependent and -independent repression activities is higher than that of the CtBP-independent domain alone. The requirement for CtBP at certain enhancers appears to reflect the need for overall higher levels of repression, rather than a requirement for an activity unique to CtBP. Thus, CtBP contributes quantitatively, rather than qualitatively, to overall repression function. The finding that both repression activities are simultaneously deployed suggests that the multiple repression activities do not function as cryptic 'backup' systems, but that each contributes quantitatively to total repressor output.

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Competition for Overlapping Sites in the Regulatory Region of the Drosophila Gene Krüppel

Cited by 133 publications

References 63 publications

Identification of a photoreceptor cell-specific nuclear receptor

Identification of a photoreceptor cell-specific nuclear receptor

Conserved and divergent aspects of terminal patterning in the beetle Tribolium castaneum

Quantitative contributions of CtBP-dependent and -independent repression activities of Knirps

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