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Regulation of gene expression by sequence-specific transcription factors is central to developmental programs and depends on the binding of transcription factors with target sites in the genome. To date, most such analyses in Caenorhabditis elegans have focused on the interactions between a single transcription factor with one or a few select target genes.(More)
1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading(More)
We have used systematic fluorescence resonance energy transfer and distance-constrained docking to define the three-dimensional structures of bacterial RNA polymerase holoenzyme and the bacterial RNA polymerase-promoter open complex in solution. The structures provide a framework for understanding sigma(70)-(RNA polymerase core), sigma(70)-DNA, and(More)
Class II CAP-dependent promoters, interacting with the RNAP ␣ subunit C-terminal domain (␣CTD) and facilitat-At Class I CAP-dependent promoters, interaction between the activating region and ␣CTD (and concomitant St. Louis, Missouri 63104 recruitment of RNAP to promoter DNA) appears to be the entire basis of transcription activation. Thus, at Class Summary(More)
We present a network framework for analyzing multi-level regulation in higher eukaryotes based on systematic integration of various high-throughput datasets. The network, namely the integrated regulatory network, consists of three major types of regulation: TF→gene, TF→miRNA and miRNA→gene. We identified the target genes and target miRNAs for a set of TFs(More)
Understanding the in vivo dynamics of protein localization and their physical interactions is important for many problems in biology. To enable systematic protein function interrogation in a multicellular context, we built a genome-scale transgenic platform for in vivo expression of fluorescent- and affinity-tagged proteins in Caenorhabditis elegans under(More)
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(More)
Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to(More)
Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were(More)
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We(More)