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Global profile of intestine-specific gene expression in C. elegans Export

International Worm Meeting (2005)

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C. elegans / WormBase's tags for this article

caenorhabditis_elegans celegans c_elegans elegans end-1 f58e102 ges-1 med-1 meeting_abstract nematode r12a14 t24d31 wormbase

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The simple body plan, many tissues, and complete genome sequence of C. elegans allow for a systems biology approach to the question of which genes specify a tissue. A global profile of tissue-specific gene expression of this organism would expand our knowledge of tissue development and maintenance, regulation of gene expression, and higher order chromosome structure. We used mRNA tagging (Roy et al.) to identify genes expressed in the intestine of the worm. Animals expressing an epitope-tagged protein that binds the poly-A tail of mRNAs (FLAG::PAB-1) from an intestine-specific promoter (ges-1) were used to immunoprecipitate (IP) FLAG::PAB-1/mRNA complexes from the intestine. Genes enriched by intestinal IP were identified with DNA microarrays. The average ranks of enrichment from 8 repeats of this experiment identified 1938 intestine-expressed genes (p<0.001). First, we compared the intestine-expressed genes to those expressed in the muscle (Roy et al.) and germline (Reinke et al.), and identified 510 genes enriched in all 3 tissues and 246 intestine-, 115 muscle-, and 219 germline-enriched genes. Second, we showed that the 1938 intestine genes were physically clustered on the chromosomes, suggesting that the order of genes in the genome is influenced by the effect of chromatin domains on gene expression. Furthermore, the commonly-expressed genes showed more chromosomal clustering than the tissue-enriched genes, suggesting that chromatin domains may influence housekeeping genes more than tissue-specific genes. Third, in order to gain further insight into the regulation of intestinal gene expression, we searched for regulatory motifs. We used a modified Gibbs sampling method called CompareProspector (Liu et al.) to identify motifs that were conserved with C. briggsae and over-represented in the 1 kb upstream region of the 1938 intestine-expressed genes. This analysis found that the promoters of the intestine genes were enriched for the consensus sequence for GATA transcription factors. We experimentally verified these results by showing that GATA motifs are required in cis and that GATA transcription factors are required in trans for expression of these intestinal genes. Previous work had shown that GATA transcription factors (med-1, end-1, etc.) are important for intestinal differentiation, and our work has identified about 800 intestinal genes that may be the direct targets of the GATA transcription factors. Liu, Y. et al. (2004). Genome Research, 14(3), 451-458. Reinke, V. et al. (2004). Development, 131(2), 311-323. Roy, P. J. et al. (2002). Nature, 418(6901), 975-979.


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