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Author Notes:

Corresponding author: Jason D. Lieb, Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. Email: jlieb@bio.unc.edu.

Conceived and designed the experiments: CMW WGK JDL.

Performed the experiments: CMW KNM.

Analyzed the data: CMW SE WGK JDL.

Wrote the paper: CMW JDL.

Designed, manufactured, and hybridized the DNA microarrays: XZ RDG.

We thank Paul Giresi, Peter Sudmant, Michael Buck, and Corey Reece for programming, help with annotations, and assistance during data analysis.

We are grateful to Susan Mango for the HTZ-1::YFP strain, X. Shirley Liu for CEAS annotation software, the Caenorhabditis Genetic Center (CGC) for strains, Shohei Mitani for the htz-1(tm2469) strain, Tom Blumenthal for helpful discussions regarding operons, Györgyi Csankovszki for helpful discussions and sharing of reagents, Susan Strome for MES-4 antibodies, and Barbara J. Meyer for DPY-27 antibodies.

XZ and RDG are employed by NimbleGen Systems, Inc., a microarray company that might profit from the publication of this paper.

NimbleGen Systems provided the microarrays.


Research Funding:

This work was supported by National Institutes of Health grant GM63102 to WGK, National Human Genome Research Institute modENCODE grant 1-U01-HG004270-01 to JDL, and V Foundation for Cancer Research Scholar award to JDL.

CMW was supported in part by National Institutes of Health training grant T32 HD046369.

The Genomic Distribution and Function of Histone Variant HTZ-1 during C. elegans Embryogenesis

Journal Title:

PLoS Genetics


Volume 4, Number 9


, Pages e1000187-e1000187

Type of Work:

Article | Final Publisher PDF


In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1) during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis.

Copyright information:

© 2008 Whittle et al.

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