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RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo


It is widely assumed that the key rate-limiting step in gene activation is the recruitment of RNA polymerase II (Pol II) to the core promoter1. Although there are well-documented examples in which Pol II is recruited to a gene but stalls2,3,4,5,6,7,8,9,10,11,12, a general role for Pol II stalling in development has not been established. We have carried out comprehensive Pol II chromatin immunoprecipitation microarray (ChIP-chip) assays in Drosophila embryos and identified three distinct Pol II binding behaviors: active (uniform binding across the entire transcription unit), no binding, and stalled (binding at the transcription start site). The notable feature of the 10% genes that are stalled is that they are highly enriched for developmental control genes, which are either repressed or poised for activation during later stages of embryogenesis. We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development.

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Figure 1: Different classes of Pol II binding profiles.
Figure 2: Whole-genome analysis of Pol II binding.
Figure 3: Confirmation of the class of genes with Pol II stalling.
Figure 4: Functional analysis of the three classes of genes.
Figure 5: Pol II profile comparison of genes in the repressed versus active state.
Figure 6: Pol II stalling at genes before activation.

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We would like to thank R. Zinzen for collecting the Toll10b, Tollrm9/rm10 and gd7 embryos, T. Volkert and J. Love for microarray experimental support and members of the Young laboratory for critical reading of the manuscript. This research was supported in part by the Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences (K.A.), US National Institutes of Health grants HG002668 and GM069676 to R.A.Y. and GM34431 to M.L., a grant by the Moore Foundation and a postdoctoral fellowship by the Human Frontier Science Program Organization (HFSPO, A.S.).

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Authors and Affiliations



J.Z. and M.L. designed the experiment. J.Z. designed the arrays and carried out the experiments and analysis. A.S., M.K. and J.Z. analyzed expression data and functional categories. J.-W.H., S.N. and K.A. carried out the permanganate footprint assays. J.Z., M.L. and R.A.Y. prepared the manuscript.

Corresponding authors

Correspondence to Michael Levine or Richard A Young.

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One of the authors (R.A.Y.) consults for Agilent Technologies.

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Zeitlinger, J., Stark, A., Kellis, M. et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat Genet 39, 1512–1516 (2007).

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