DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).

Department of Animal Science, Aarhus University, Aarhus, Denmark Viral hemorrhagic septicaemia virus (VHSV) is an important viral pathogen in European rainbow trout farming. Isolates from wild marine fish and freshwater trout farms show highly different virulence profiles: isolates from marine fish species cause little or no mortality in rainbow trout following experimental waterborne challenge, whilst challenge with rainbow trout isolates results in high levels of mortality. Phylogenetic analyses have revealed that the highly virulent trout-derived isolates from freshwater farms have evolved from VHSV isolates from marine fish host species over the past 60 years. Recent isolates from rainbow trout reared in marine zones show intermediate virulence. The present study aimed to identify molecular virulence markers that could be used to classify VHSV isolates according to their ability to cause disease in rainbow trout. By a reverse genetics approach using a VHSV-related novirhabdovirus [infectious hematopoietic necrosis virus (IHNV)], four chimaeric IHNV-VHSV recombinant viruses were generated. These chimaeric viruses included substitution of the IHNV glyco-(G) or non-structural (Nv) protein with their counterparts from either a trout-derived or a marine VHSV strain. Comparative challenge experiments in rainbow trout fingerlings revealed similar levels of survival induced by the recombinant (r)IHNV-VHSV chimaeric viruses regardless of whether the G or Nv genes originated from VHSV isolated from a marine fish species or from rainbow trout. Interestingly, recombinant IHNV gained higher virulence following substitution of the G gene with those of the VHSV strains, whilst the opposite was the case following substitution of the Nv genes. INTRODUCTIONUntil 1988, viral hemorrhagic septicaemia virus (VHSV) was recognized as the causative agent of viral hemorrhagic septicaemia (VHS) affecting only European freshwater fish species, mainly rainbow trout (Oncorhynchus mykiss). As a result of infection, mortality rates are as high as 90 %, resulting in serious economic losses to the aquaculture industry (Nylin & Olesen, 2001;Smail, 1999). VHSV was then isolated for the first time in North America from ascending Chinook and coho salmon (Brunson, 1989;Hopper, 1989) and soon after in wild cod (Smail, 1995).The latter confirmed VHSV in the marine environment of Europe, and altered the view on an earlier isolate from cod caught in the Baltic Sea previously in 1979 (Jensen & Larsen, 1979). Surveys in European waters found an extensive VHSV reservoir involving many marine fish species, and by 2005, VHSV had been isolated from 48 different species (Skall et al., 2005). This number has increased since, in particular due to the recent emergence of VHSV in the North American Great Lakes where at least 28 freshwater species have been shown to be VHSV susceptible (USDA-APHIS, 2008a, b).VHSV is a negative-sense ssRNA in the genus Novirhabdovirus and family Rhabdoviridae (Van Regenmortel et al., 2000). To date, novirhabdoviruses have been is...