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cis-Regulatory Complexity within a Large Non-Coding Region in the Drosophila Genome

Author

Listed:
  • Mukta Kundu
  • Alexander Kuzin
  • Tzu-Yang Lin
  • Chi-Hon Lee
  • Thomas Brody
  • Ward F Odenwald

Abstract

Analysis of cis-regulatory enhancers has revealed that they consist of clustered blocks of highly conserved sequences. Although most characterized enhancers reside near their target genes, a growing number of studies have shown that enhancers located over 50 kb from their minimal promoter(s) are required for appropriate gene expression and many of these ‘long-range’ enhancers are found in genomic regions that are devoid of identified exons. To gain insight into the complexity of Drosophila cis-regulatory sequences within exon-poor regions, we have undertaken an evolutionary analysis of 39 of these regions located throughout the genome. This survey revealed that within these genomic expanses, clusters of conserved sequence blocks (CSBs) are positioned once every 1.1 kb, on average, and that a typical cluster contains multiple (5 to 30 or more) CSBs that have been maintained for at least 190 My of evolutionary divergence. As an initial step toward assessing the cis-regulatory activity of conserved clusters within gene-free genomic expanses, we have tested the in-vivo enhancer activity of 19 consecutive CSB clusters located in the middle of a 115 kb gene-poor region on the 3rd chromosome. Our studies revealed that each cluster functions independently as a specific spatial/temporal enhancer. In total, the enhancers possess a diversity of regulatory functions, including dynamically activating expression in defined patterns within subsets of cells in discrete regions of the embryo, larvae and/or adult. We also observed that many of the enhancers are multifunctional–that is, they activate expression during multiple developmental stages. By extending these results to the rest of the Drosophila genome, which contains over 70,000 non-coding CSB clusters, we suggest that most function as enhancers.

Suggested Citation

  • Mukta Kundu & Alexander Kuzin & Tzu-Yang Lin & Chi-Hon Lee & Thomas Brody & Ward F Odenwald, 2013. "cis-Regulatory Complexity within a Large Non-Coding Region in the Drosophila Genome," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-14, April.
  • Handle: RePEc:plo:pone00:0060137
    DOI: 10.1371/journal.pone.0060137
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    References listed on IDEAS

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    1. Len A. Pennacchio & Nadav Ahituv & Alan M. Moses & Shyam Prabhakar & Marcelo A. Nobrega & Malak Shoukry & Simon Minovitsky & Inna Dubchak & Amy Holt & Keith D. Lewis & Ingrid Plajzer-Frick & Jennifer , 2006. "In vivo enhancer analysis of human conserved non-coding sequences," Nature, Nature, vol. 444(7118), pages 499-502, November.
    2. Nicolás Frankel & Gregory K. Davis & Diego Vargas & Shu Wang & François Payre & David L. Stern, 2010. "Phenotypic robustness conferred by apparently redundant transcriptional enhancers," Nature, Nature, vol. 466(7305), pages 490-493, July.
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