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Distinct in vivo requirements for establishment versus maintenance of transcriptional repression

Nature Genetics volume 32, pages 206–210 (2002)Cite this article

Abstract

Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashion to Runt-mediated repression, that there are two distinct steps in the repression of en by Runt. The initial establishment of repression is sensitive to the dosage of the zinc-finger transcription factor Tramtrack. By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage. The distinction between establishment and maintenance is confirmed by experiments with Runt derivatives that are impaired specifically for either co-repressor interaction or DNA binding. Other transcription factors can also establish repression in Rpd3-deficient embryos, which indicates that the distinction between establishment and maintenance may be a general feature of eukaryotic transcriptional repression.

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Figure 1: Runt is a potent repressor of en.
Figure 2: Dose-dependent maternal effects on establishment and maintenance of en repression.
Figure 3: Rpd3-independent repression by Runt, Sloppy-paired 2 or Even-skipped.
Figure 4: Groucho recruitment and DNA binding are required for maintenance of en repression.
Figure 5: Genetics of establishment and maintenance of repression by Runt.

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Acknowledgements

We thank the Drosophila Stock Center in Bloomington and our colleagues who provided Drosophila stocks and plasmid DNAs; S. Kramer and L.-H. Li for the p[UAS–run[CK]] construct and the initial UAS–run[CK] transformant line, respectively; X. Ning for help with generating the UAS–run[Δ8] construct and transformant lines; T. Kalkan for help with characterizing the effects of deficiency chromosomes; and J. Landry and members of the Gergen laboratory for comments on the manuscript. This work was supported by grants from the NIH and the NSF to J.P.G.

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Author notes

  1. John C. Wheeler

    Present address: The Rothberg Institute for Childhood Diseases, Guilford, Connecticut, USA

  2. John C. Wheeler and Christine VanderZwan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, Stony Brook University, Stony Brook, 11794-5140, New York, USA

    John C. Wheeler, Christine VanderZwan, Xiaoti Xu, Deborah Swantek, W. Daniel Tracey & J. Peter Gergen

  2. Graduate Program in Genetics, Stony Brook University, Stony Brook, 11794-5140, New York, USA

    Christine VanderZwan & W. Daniel Tracey

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Correspondence to J. Peter Gergen.

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Wheeler, J., VanderZwan, C., Xu, X. et al. Distinct in vivo requirements for establishment versus maintenance of transcriptional repression. Nat Genet 32, 206–210 (2002). https://doi.org/10.1038/ng942

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