title: Genome-wide analysis of promoter architecture in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 97420, USA.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Hoskins
authors.forename: Jane M
authors.initials: JM
authors.lastname: Landolin
authors.forename: James B
authors.initials: JB
authors.lastname: Brown
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Sandler
authors.forename: Hazuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Charles
authors.initials: C
authors.lastname: Yu
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Booth
authors.forename: Dayu
authors.initials: D
authors.lastname: Zhang
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Wan
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Nathan
authors.initials: N
authors.lastname: Boley
authors.forename: Justen
authors.initials: J
authors.lastname: Andrews
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Kaufman
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bickel
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D049750:Genome, Insect / Q000235:genetics*; D055106:Genome-Wide Association Study; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
chemical_list: D020413:3' Untranslated Regions