TITLE

Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets

AUTHOR(S)
Chowdhury, Shankar R; King, Dale E; Willing, Benjamin P; Band, Mark R; Beever, Jonathan E; Lane, Adrienne B; Loor, Juan J; Marini, Juan C; Rund, Laurie A; Schook, Lawrence B; Van Kessel, Andrew G; Gaskins, H Rex
PUB. DATE
January 2007
SOURCE
BMC Genomics;2007, Vol. 8, p215
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: To gain insight into host-microbe interactions in a piglet model, a functional genomics approach was used to address the working hypothesis that transcriptionally regulated genes associated with promoting epithelial barrier function are activated as a defensive response to the intestinal microbiota. Cesarean-derived germ-free (GF) newborn piglets were colonized with adult swine feces, and villus and crypt epithelial cell transcriptomes from colonized and GF neonatal piglets were compared using laser-capture microdissection and high-density porcine oligonucleotide microarray technology. Results: Consistent with our hypothesis, resident microbiota induced the expression of genes contributing to intestinal epithelial cell turnover, mucus biosynthesis, and priming of the immune system. Furthermore, differential expression of genes associated with antigen presentation (pan SLA class I, B2M, TAP1 and TAPBP) demonstrated that microbiota induced immune responses using a distinct regulatory mechanism common for these genes. Specifically, gene network analysis revealed that microbial colonization activated both type I (IFNAR) and type II (IFNGR) interferon receptor mediated signaling cascades leading to enhanced expression of signal transducer and activator of transcription 1 (STAT1), STAT2 and IFN regulatory factor 7 (IRF7) transcription factors and the induction of IFN-inducible genes as a reflection of intestinal epithelial inflammation. In addition, activated RNA expression of NF-kappa-B inhibitor alpha (NFκBIA; a.k.a I-kappa-B-alpha, IKBκ) and toll interacting protein (TOLLIP), both inhibitors of inflammation, along with downregulated expression of the immunoregulatory transcription factor GATA binding protein-1 (GATA1) is consistent with the maintenance of intestinal homeostasis. Conclusion: This study supports the concept that the intestinal epithelium has evolved to maintain a physiological state of inflammation with respect to continuous microbial exposure, which serves to sustain a tight intestinal barrier while preventing overt inflammatory responses that would compromise barrier function.
ACCESSION #
28858862

 

Related Articles

  • Experimental advances in the characterization of metazoan gene regulatory networks. Deplancke, Bart // Briefings in Functional Genomics & Proteomics;Jan2009, Vol. 8 Issue 1, p12 

    Gene regulatory networks (GRNs) play a vital role in metazoan development and function, and deregulation of these networks is often implicated in disease. GRNs depict the dynamic interactions between genomic and regulatory state components. The genomic components comprise genes and their...

  • ITFP: an integrated platform of mammalian transcription factors. Guangyong Zheng; Kang Tu; Qing Yang; Yun Xiong; Chaochun Wei; Lu Xie; Yangyong Zhu; Yixue Li // Bioinformatics;Oct2008, Vol. 24 Issue 20, p2416 

    Summary: Investigation of transcription factors (TFs) and their downstream regulated genes (targets) is a significant issue in post-genome era, which can provide a brand new vision for some vital biological process. However, information of TFs and their targets in mammalian is far from...

  • Cancer genomics: Complete coverage? Goymer, Patrick // Nature Reviews Genetics;Mar2006, Vol. 7 Issue 3, p1 

    Discusses research being done on a global map of p53 transcription-factor binding sites in the human genome. Reference to a study by C. L. Wei et al, published in a 2006 issue of "Cell"; Use of the paired-end ditag sequencing on p53; Observation on the position of the binding site between genes...

  • Recent Computational Approaches to Understand Gene Regulation: Mining Gene Regulation In Silico. Abnizova, I.; Subhankulova, T.; Gilks, W. R. // Current Genomics;Apr2007, Vol. 8 Issue 2, p79 

    This paper reviews recent computational approaches to the understanding of gene regulation in eukaryotes. Cis-regulation of gene expression by the binding of transcription factors is a critical component of cellular physiology. In eukaryotes, a number of transcription factors often work together...

  • From sequence to structure and back again: approaches for predicting protein-DNA binding. Höglund, Annette; Kohlbacher, Oliver // Proteome Science;2004, Vol. 2, p3 

    Gene regulation in higher organisms is achieved by a complex network of transcription factors (TFs). Modulating gene expression and exploring gene function are major aims in molecular biology. Furthermore, the identification of putative target genes for a certain TF serve as powerful tools for...

  • Getting connected in the globin interactome. Ragoczy, Tobias; Groudine, Mark // Nature Genetics;Jan2010, Vol. 42 Issue 1, p16 

    A new study provides compelling evidence that transcriptional regulation and three-dimensional genomic architecture are linked. The alpha- and beta-globin loci associate with hundreds of active genes across the genome at transcription factories in erythroid cells, and specialized Klf1-containing...

  • Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Schoenfelder, Stefan; Sexton, Tom; Chakalova, Lyubomira; Cope, Nathan F.; Horton, Alice; Andrews, Simon; Kurukuti, Sreenivasulu; Mitchell, Jennifer A.; Umlauf, David; Dimitrova, Daniela S.; Eskiw, Christopher H.; Yanquan Luo; Chia-Lin Wei; Yijun Ruan; Bieker, James J.; Fraser, Peter // Nature Genetics;Jan2010, Vol. 42 Issue 1, p53 

    The discovery of interchromosomal interactions in higher eukaryotes points to a functional interplay between genome architecture and gene expression, challenging the view of transcription as a one-dimensional process. However, the extent of interchromosomal interactions and the underlying...

  • Distinct requirements for C.elegans TAFIIs in early embryonic transcription. Walker, Amy K.; Rothman, Joel H.; Yang Shi; Blackwell, T. Keith // EMBO Journal;9/15/2001, Vol. 20 Issue 18, p5269 

    TAFIIs are conserved components of the TFIID, TFTC and SAGA-related mRNA transcription complexes. In yeast (y), yTAFII17 is required broadly for transcription, but various other TAFIIs appear to have more specialized functions. It is important to determine how TAFIIs contribute to transcription...

  • Binding Site Graphs: A New Graph Theoretical Framework for Prediction of Transcription Factor Binding Sites. Reddy, Timothy E.; DeLisi, Charles; Shakhnovich, Boris E. // PLoS Computational Biology;May2007, Vol. 3 Issue 5, pe90 

    Computational prediction of nucleotide binding specificity for transcription factors remains a fundamental and largely unsolved problem. Determination of binding positions is a prerequisite for research in gene regulation, a major mechanism controlling phenotypic diversity. Furthermore, an...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics