Telomeric Position Effect Variegation in Saccharomyces cerevisiae by Caenorhabditis elegans Linker Histones Suggests a Mechanistic Connection between Germ Line and Telomeric Silencing

Abstract

Linker histones are nonessential for the life of single-celled eukaryotes. Linker histones, however, can be important components of specific developmental programs in multicellular animals and plants. For Caenorhabditis elegans a single linker histone variant (H1.1) is essential in a chromatin silencing process which is crucial for the proliferation and differentiation of the hermaphrodite germ line. In this study we analyzed the whole linker histone complement of C. elegans by telomeric position effect variegation in budding yeast. In this assay an indicator gene (URA3) placed close to the repressive telomeric chromatin structure is subject to epigenetically inherited gene inactivation. Just one out of seven C. elegans linker histones (H1.1) was able to enhance the telomeric position effect in budding yeast. Since these results reflect the biological function of H1.1 in C. elegans, we suggest that chromatin silencing in C. elegans is governed by molecular mechanisms related to the telomere-dependent silencing in budding yeast. We confirmed this hypothesis by testing C. elegans homologs of three yeast genes which are established modifiers of the yeast telomeric chromatin structure (SIR2, SET1, and RAD17) for their influence on repeat-dependent transgene silencing for C. elegans.

ACKNOWLEDGMENTS

We thank Ulrich Grossbach for his support of the C. elegans group, Sabine Steinhoff and Bettina Schulze for the establishment of the basic yeast protocols, Werner Albig for the yeast immunofluorescence protocol, Hans Dieter Schmitt for the yeast strain S35P-5A, Daniel E. Gottschling for the yeast strains UCC3505 and UCC7007-1, Yuji Kohara, Mishima, for the yk cDNA clones, Harald Kolmar for performing the flow cytometry, Bettina Schulze for critically reading the manuscript, and the students of our summer 1998 and 2000 advanced level practical course in developmental biology for their contributions to this project. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. We acknowledge the excellent technical assistance of Sabine Pitzel and Barbara Lage.

This work was supported by the Deutsche Forschungsgemeinschaft grant GRK 242-2 (Graduiertenkolleg “Molekulare Genetik der Entwicklung”) to U. Grossbach, grant SCHU 1033/3-3 to E. Schulze and U. Grossbach, and grant SFB271 A14 to E. Schulze.