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X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation

Nature Genetics volume 39, pages 403–408 (2007)Cite this article

Abstract

Among organisms with chromosome-based mechanisms of sex determination, failure to equalize expression of X-linked genes between the sexes is typically lethal. In C. elegans, XX hermaphrodites halve transcription from each X chromosome to match the output of XO males1. Here, we mapped the binding location of the condensin homolog DPY-27 and the zinc finger protein SDC-3, two components of the C. elegans dosage compensation complex (DCC)2,3. We observed strong foci of DCC binding on X, surrounded by broader regions of localization. Binding foci, but not adjacent regions of localization, were distinguished by clusters of a 10-bp DNA motif, suggesting a recruitment-and-spreading mechanism for X recognition. The DCC was preferentially bound upstream of genes, suggesting modulation of transcriptional initiation and polymerase-coupled spreading. Stronger DCC binding upstream of genes with high transcriptional activity indicated a mechanism for tuning DCC activity at specific loci. These data aid in understanding how proteins involved in higher-order chromosome dynamics can regulate transcription at individual loci.

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Figure 1: High-resolution localization of the DCC authenticates binding at putative recruitment elements and uncovers new targets.
Figure 2: SDC-3 and DPY-27 bind specifically to the X with distinct modes of distribution.
Figure 3: A distinct class of DCC localization foci along X.
Figure 4: A stereotypic 10-bp DNA sequence motif is enriched in foci of DCC binding.
Figure 5: The DCC preferentially binds upstream of genes and is positively correlated with transcriptional activity.

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Acknowledgements

We thank A.B. Nobel (University of North Carolina) for providing statistical guidance, especially regarding the clustering of DCC binding peaks. This work was supported by the Carolina Center for Genome Sciences and by a grant awarded to J.D.L. from The V Foundation for Cancer Research.

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Authors and Affiliations

  1. Department of Biology and Carolina Center for the Genome Sciences, 202 Fordham Hall, University of North Carolina at Chapel Hill, Chapel Hill, 27599-3280, North Carolina, USA

    Sevinc Ercan, Paul G Giresi, Christina M Whittle & Jason D Lieb

  2. NimbleGen Systems, Inc., 1 Science Court, Madison, 53711, Wisconsin, USA

    Xinmin Zhang & Roland D Green

Authors
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Contributions

This study was designed by S.E. and J.D.L. S.E. conducted the experiments. S.E., P.G.G., C.M.W. and J.D.L. conducted the data analysis. X.Z and R.D.G. designed, manufactured, and hybridized the DNA microarrays. S.E. and J.D.L. wrote the paper.

Corresponding author

Correspondence to Jason D Lieb.

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Competing interests

X.Z. and R.D.G. are employed by NimbleGen Systems, a microarray company that might profit from the publication of this paper.

Supplementary information

Supplementary Fig. 1

DCC binding peak distribution. (PDF 287 kb)

Supplementary Fig. 2

DCC binding at previously defined rex loci. (PDF 402 kb)

Supplementary Fig. 3

The relationship between DCC binding and the distribution of the putative DCC recruitment motif. (PDF 295 kb)

Supplementary Fig. 4

The DCC preferentially binds to the 5′ region of genes and is positively correlated with transcriptional activity. (PDF 999 kb)

Supplementary Fig. 5

The predictive value of the 10-bp putative DCC recruitment motif identified in this study versus putative DCC recruitment motifs identified previously. (PDF 409 kb)

Supplementary Table 1

Sites of autosomal DCC enrichment and X-linked DCC foci. (PDF 10 kb)

Supplementary Methods (PDF 37 kb)

Supplementary Note (PDF 61 kb)

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Ercan, S., Giresi, P., Whittle, C. et al. X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation. Nat Genet 39, 403–408 (2007). https://doi.org/10.1038/ng1983

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