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Genome-wide analysis of promoter architecture in Drosophila melanogaster.

Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.

Pubmed ID: 21177961

Authors

  • Hoskins RA
  • Landolin JM
  • Brown JB
  • Sandler JE
  • Takahashi H
  • Lassmann T
  • Yu C
  • Booth BW
  • Zhang D
  • Wan KH
  • Yang L
  • Boley N
  • Andrews J
  • Kaufman TC
  • Graveley BR
  • Bickel PJ
  • Carninci P
  • Carlson JW
  • Celniker SE

Journal

Genome research

Publication Data

February 17, 2011

Associated Grants

  • Agency: NHGRI NIH HHS, Id: U01 HG004271
  • Agency: NHGRI NIH HHS, Id: U01 HG004271

Mesh Terms

  • 3' Untranslated Regions
  • Animals
  • Chromosome Mapping
  • Computational Biology
  • Drosophila melanogaster
  • Expressed Sequence Tags
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Insect
  • Genome-Wide Association Study
  • Promoter Regions, Genetic
  • Transcription Initiation Site