The ModERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors.

To develop a catalog of regulatory sites in two major model organisms, Drosophila melanogaster and Caenorhabditis elegans, the modERN (model organism Encyclopedia of Regulatory Networks) consortium has systematically assayed the binding sites of transcription factors (TFs). Combined with data produced by our predecessor, modENCODE (Model Organism ENCyclopedia Of DNA Elements), we now have data for 262 TFs identifying 1.23 M sites in the fly genome and 217 TFs identifying 0.67 M sites in the worm genome. Because sites from different TFs are often overlapping and tightly clustered, they fall into 91,011 and 59,150 regions in the fly and worm, respectively, and these binding sites span as little as 8.7 and 5.8 Mb in the two organisms. Clusters with large numbers of sites (so-called high occupancy target, or HOT regions) predominantly associate with broadly expressed genes, whereas clusters containing sites from just a few factors are associated with genes expressed in tissue-specific patterns. All of the strains expressing GFP-tagged TFs are available at the stock centers, and the chromatin immunoprecipitation sequencing data are available through the ENCODE Data Coordinating Center and also through a simple interface (http://epic.gs.washington.edu/modERN/) that facilitates rapid accessibility of processed data sets. These data will facilitate a vast number of scientific inquiries into the function of individual TFs in key developmental, metabolic, and defense and homeostatic regulatory pathways, as well as provide a broader perspective on how individual TFs work together in local networks and globally across the life spans of these two key model organisms.

Regulatory analysis of the C. elegans genome with spatiotemporal resolution.

Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.

Comparative analysis of regulatory information and circuits across distant species.

Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.

Injuries in team sport tournaments during the 2004 Olympic Games.

BACKGROUND: Several authors have analyzed the incidence of injuries in a given sport, but only a few have examined the exposure-related incidence of injuries in different types of sports using the same methodology. PURPOSE: Analysis of the incidence, circumstances, and characteristics of injuries in different team sports during the 2004 Olympic Games. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: During the 2004 Olympic Games, injuries in 14 team sport tournaments (men's and women's soccer, men's and women's handball, men's and women's basketball, men's and women's field hockey, baseball, softball, men's and women's water polo, and men's and women's volleyball) were analyzed. After each match, the physician of the participating teams or the official medical representative of the sport completed a standardized injury report form. The mean response rate was 93%. RESULTS: A total of 377 injuries were reported from 456 matches, an incidence of 0.8 injuries per match (95% confidence interval, 0.75-0.91) or 54 injuries per 1000 player matches (95% confidence interval, 49-60). Half of all injuries affected the lower extremity; 24% involved the head or neck. The most prevalent diagnoses were head contusion and ankle sprain. On average, 78% of injuries were caused by contact with another player. However, a significantly higher percentage of noncontact (57%) versus contact injuries (37%) was expected to prevent the player from participating in his or her sport. Significantly more injuries in male players (46%) versus female players (35%) were expected to result in absence from match or training. The incidence, diagnosis, and causes of injuries differed substantially between the team sports. CONCLUSION: The risk of injury in different team sports can be compared using standardized methodology. Even if the incidence and characteristics of injuries are not identical in all sports, prevention of injury and promotion of fair play are relevant topics for almost all team sports.