We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor–binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor–binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

Chromosome segregation at meiosis I depends on pairing and crossing-over between homologs. In most eukaryotes, pairing culminates with formation of the proteinaceous synaptonemal complex (SC). In budding yeast, recombination initiates through double-strand DNA breaks (DSBs) and is thought to be essential for SC formation. Here, we examine whether this mechanism for initiating meiotic recombination is conserved, and we test the dependence of homologous chromosome synapsis on recombination in C. elegans. We find that a homolog of the yeast DSB-generating enzyme, Spo11p, is required for meiotic exchange in this metazoan, and that radiation-induced breaks partially alleviate this dependence. Thus, initiation of recombination by DSBs is apparently conserved. However, homologous synapsis is independent of recombination in the nematode, since it occurs normally in a C. elegans spo-11 null mutant.

Summary Sexual reproduction requires the unique cell division called meiosis, in which a diploid cell undergoes a reductional division to generate haploid gametes. A hallmark of meiotic prophase is the formation of pairwise linkages between homologous chromosomes, which later enable them to segregate from each other. In most organisms the pairing of homologous chromosomes is reinforced by synapsis, the polymerization of the synaptonemal complex (SC) between paired chromosome axes. The primary questions addressed here are: 1) how pairing is accomplished and 2) how synapsis is regulated so that it occurs selectively between homologs. We provide evidence that a connection between the chromosomes and the microtubule cytoskeleton via a bridge across the nuclear envelope is critical for both of these mechanisms. Our results indicate the existence of a mechanism that uses dynein to assess homology before licensing SC polymerization. The molecular components of this mechanism are conserved from fungi to mammals.