Steven M. Johnson et al. (2007) International Worm Meeting "Toward a high-resolution nucleosome position map of the Caenorhabditis elegans genome."

Frederick J. Tan, Arend Sidow, Thaisan Tonthat, Heather L. McCullough, Anton Valouev, Kathy Zeng, Heather Peckham, Gina Costa, Andrew Fire, Daniel P. Riordan, Steven M. Johnson, Joel Malek, Jeremy Stuart, Kevin McKernan, Jeffrey Ichikawa, Swati Ranade

[International Worm Meeting, 2007]

We are working toward a detailed structural and dynamic picture of C. elegans chromatin. Nucleosome positions within the chromatin landscape are known to serve as a major determinant of DNA accessibility to transcription factors and other interacting components. To delineate nucleosomal patterns in C. elegans, we are carrying out a genome-wide analysis in which DNA fragments corresponding to nucleosome cores are liberated using Micrococcal nuclease. Sequence analysis of an initial set of putative nucleosome cores obtained in this manner from a mixed-stage population of C. elegans reveals a combined picture of flexibility and constraint in nucleosome positioning. As had previously been observed in studies of individual loci in diverse biological systems, we observe areas in the genome where nucleosomes can adopt a wide variety of positions in a given region, areas with little or no nucleosome coverage, and areas where nucleosomes reproducibly adopt a specific positional pattern. In addition to illuminating numerous aspects of chromatin structure for C. elegans, this analysis provides a reference from which to begin an investigation of relationships between the nucleosomal pattern, chromosomal architecture, and lineage-based gene activity on a genome-wide scale. We are currently extending this analysis using ultra-high-throughput sequencing techniques analyzing the genomic positions of millions of nucleosome cores toward the end of producing a high-resolution nucleosome position map of the C. elegans genome.

Keith A Boroevich et al. (2004) West Coast Worm Meeting "Identification of Regulatory Elements in Caenorhabditis elegans using Orthology Biased Gibbs Sampling"

Steven JM Jones, David L Baillie, Keith A Boroevich

[West Coast Worm Meeting, 2004]

Much attention has recently been placed on the problem of identification of gene regulatory sequences. Two main computational approaches exist: 1) identification of sequences that share similarity to known regulatory elements, and 2) de novo identification of common motifs in a set of co-regulated genes. Orthology Biased Gibbs Sampling (OrBS) applies a modification of the Gibbs Sampler put forth by Lawrence, Altschult et al . 1 in a attempt to solve this problem. Additional features include analysis of negative strand, multiple (or no) occurrences of a motif in any given sequence and identification of multiple unique motifs, all of which have appeared in previous incarnations of the Gibbs Sampler. The unique feature of OrBS is the use of comparative genomics as an informative prior and in the calculation of motif probability. OrBS will be applied to the identification of regulatory elements C. elegans . Clustering of spatially co-regulated genes as defined by the C. elegans Gene Expression Project (see Johnsen et al . poster). This data is more amenable to regulatory element detection than the more common microarray data because the sequence in which a cis -acting element may reside is strictly defined. Interspecies sequence conservation will be identified through alignment of the C. elegans gene promoter region to the promoter region of the C. briggsae ortholog using LAGAN 2 . Predicted regulatory elements will be verified in vivo using site directed mutagenesis and promoter::GFP fusions. References: 1 Lawrence CE, Altschul SF, Boguski MS, Liu JS, Neuwald AF, Wootton JC. (1993). Science 262: 208-214. 2 Brudno M, Do C, Cooper G, Kim MF, Davydov E, Green ED, Sidow A, Batzoglou S. (2003). Genome Research 13: 721-731.