Puffs and gene regulation — molecular insights into the <i>Drosophila</i> ecdysone regulatory hierarchy

Thummel, Carl S.

doi:10.1002/bies.950121202

Cited by 64 publications

(42 citation statements)

References 40 publications

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“…Thus, we predict that the multiple transcripts encoded by the BR-C and E75 will be expressed in a temporal pattern determined by the lengths of their transcription units and the ecdysone concentrations required for their activation and repression. Consistent with this, both of these early genes contain nested promoters spanning unusually long transcribed regions, up to 100 kb in length (Chao and Guild 1986;Feigl et al 1989;Galcerfin et al 1990;Segraves and Hogness 1990;Thummel 1990). As with E74, the E75 transcripts have distinct temporal responses to a high concentration of ecdysone.…”

Section: Future Considerationsmentioning

confidence: 72%

Ecdysone coordinates the timing and amounts of E74A and E74B transcription in Drosophila.

Karim¹,

Thummel²

1991

Genes Dev.

143

100

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Pulses of the steroid hormone ecdysone function as temporal signals to coordinate the development of both larval and adult tissues in Drosophila. Ecdysone acts by triggering a genetic regulatory hierarchy that can be visualized as puffs in the larval polytene chromosomes. In an effort to understand how the ecdysone signal is transduced to result in sequential gene activation, we are studying the transcriptional control of E74, an early gene that appears to play a regulatory role in the hierarchy. Northern blot analysis of RNA isolated from staged animals or cultured organs was used to characterize the effects of ecdysone on E74 transcription. Ecdysone directly activates both E74A and E74B promoters. E74B mRNA precedes that of E74A, each mRNA appearing with delay times that agree with their primary transcript lengths and our previous transcription elongation rate measurement of -1.1 kb/min. The earlier appearance of E74B transcripts is enhanced by its activation at an -25-fold lower ecdysone concentration than E74A. E74B is further distinguished from E74A by its repression at a significantly higher ecdysone concentration than that required for its induction, close to the concentration required for E74A activation. These regulatory properties lead to an ecdysone-induced switch in E74 expression, with an initial burst of E74B transcription followed by a burst of E74A transcription. We also show that the patterns of ecdysone-induced E74A and E74B transcription vary in four ecdysone target tissues. These studies provide a means to translate the profile of a hormone pulse into different amounts and times of regulatory gene expression that, in turn, could direct different developmental responses in a temporally and spatially regulated manner.[Key Words: Ecdysone; transcription; metamorphosis; Drosophila; timing; steroid hormones] Received January 16, 1991; revised version accepted March 15, 1991.Steroid hormones provide higher organisms with a systemic signaling system that coordinates the growth and development of different tissues. In the fruit fly, Drosophila melanogaster, this function is provided by the steroid hormone 20-hydroxyecdysone (henceforth referred to as ecdysone), which acts throughout the life cycle to synchronize tissue-specific developmental changes (Richards 1981a). Pulses of ecdysone are released into the hemolymph during each of the six developmental stages of Drosophila: (1) in the middle of embryogenesis, (2,3) preceding the first and second-instar larval molts, (4) at the beginning of metamorphosis in late third-instar larvae, (5)preceding head eversion in prepupae, and (6) during pupal development (Richards 1981b). The most extensively studied pulse of ecdysone, at the onset of metamorphosis, serves as a temporal cue to synchronize a complex pattern of behavioral, genetic, and morphological changes that culminates in the formation of the adult fly. In triggering metamorphosis, ecdysone activates two divergent developmental pathways: The larval tissues are histolyzed, having served their functi...

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Section: Future Considerationsmentioning

confidence: 72%

Ecdysone coordinates the timing and amounts of E74A and E74B transcription in Drosophila.

Karim¹,

Thummel²

1991

Genes Dev.

143

100

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“…Metamorphosis in insects, particularly Drosophila, is also controlled by a member of the nuclear receptor family, the ecdysone receptor. Extensive genetic and molecular analyses have demonstrated that a complex gene regulation cascade regulates the metamorphic transformations and the existence of feedback mechanisms involving transcription factors encoded by ecdysone target genes (96,97). Such feedbacks appear also to exist during amphibian metamorphosis as a recent study has shown that a TH-induced transcription factor can bind to the TH-dependent promoter of the X. laevis TRbA genes to regulate TRb expression (98).…”

Section: Discussionmentioning

confidence: 99%

Dual Functions of Thyroid Hormone Receptors in Vertebrate Development: The Roles of Histone-Modifying Cofactor Complexes

Shi

2009

Thyroid

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Thyroid hormone (TH) receptor (TR) plays critical roles in vertebrate development. Transcription studies have shown that TR activates or represses TH-inducible genes by recruiting coactivators or corepressors in the presence or absence of TH, respectively. However, the developmental roles of these TR cofactors remain largely unexplored. Frog metamorphosis is totally dependent on TH and mimics the postembryonic period in mammalian development during which TH levels are also high. We have previously proposed a dual function model for TR in the development of the anuran Xenopus laevis. That is, unliganded TR recruits corepressors to THinducible genes in premetamorphic tadpoles to repress these genes and prevent premature metamorphic changes and subsequently, when TH becomes available, liganded TR recruits coactivators to activate these same genes, leading to metamorphosis. Over the years, we and others have used molecular and genetic approaches to demonstrate the importance of the dual functions of TR in Xenopus laevis. In particular, unliganded TR has been shown to recruit histone deacetylase-containing corepressor complexes in premetamorphic tadpoles to control metamorphic timing. In contrast, metamorphosis requires TH-bound TR to recruit coactivator complexes containing histone acetyltransferases and methyltransferases to activate transcription. Furthermore, the concentrations of coactivators appear to regulate the rate of metamorphic progression. Studies in mammals also suggest that the dual function model for TR is conserved across vertebrates.

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“…These polytene puffs are cytologically visible structures that appear and recede in a temporal pattern that reflects increased and decreased transcription, respectively, of loci within the puffs (for review, see Thummel 1990). Previous studies demonstrated that Pol IIo localizes to puffs (Weeks et al 1993).…”

Section: Spt5 and Spt6 Colocalize With Pol Iio On Drosophila Polytenementioning

confidence: 99%

Spt5 and Spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster

Kaplan¹,

Morris²,

Wu³

et al. 2000

Genes Dev.

213

180

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The Spt4, Spt5, and Spt6 proteins are conserved throughout eukaryotes and are believed to play critical and related roles in transcription. They have a positive role in transcription elongation in Saccharomyces cerevisiae and in the activation of transcription by the HIV Tat protein in human cells. In contrast, a complex of Spt4 and Spt5 is required in vitro for the inhibition of RNA polymerase II (Pol II) elongation by the drug DRB, suggesting also a negative role in vivo. To learn more about the function of the Spt4/Spt5 complex and Spt6 in vivo, we have identified Drosophila homologs of Spt5 and Spt6 and characterized their localization on Drosophila polytene chromosomes. We find that Spt5 and Spt6 localize extensively with the phosphorylated, actively elongating form of Pol II, to transcriptionally active sites during salivary gland development and upon heat shock. Furthermore, Spt5 and Spt6 do not colocalize widely with the unphosphorylated, nonelongating form of Pol II. These results strongly suggest that Spt5 and Spt6 play closely related roles associated with active transcription in vivo.

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Puffs and gene regulation — molecular insights into the Drosophila ecdysone regulatory hierarchy

Cited by 64 publications

References 40 publications

Ecdysone coordinates the timing and amounts of E74A and E74B transcription in Drosophila.

Ecdysone coordinates the timing and amounts of E74A and E74B transcription in Drosophila.

Dual Functions of Thyroid Hormone Receptors in Vertebrate Development: The Roles of Histone-Modifying Cofactor Complexes

Spt5 and Spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster

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