Promoter shape varies across populations and affects promoter evolution and expression noise
| Autor: | Matthew Stephens, Ignacio E. Schor, David A. Garfield, Ewan Birney, Heejung Shim, Francesco Paolo Casale, Eileen E. M. Furlong, Oliver Stegle, Jacob F. Degner, Enrico Cannavò, Dermot Harnett |
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| Rok vydání: | 2017 |
| Předmět: |
epistasis
0301 basic medicine transcriptional start site Transcription Genetic Otras Ciencias Biológicas Quantitative Trait Loci regulatory QTL Population genetics Biology eQTL Ciencias Biológicas 03 medical and health sciences core promoter Transcription (biology) Genetic variation Gene expression Genetics Animals Promoter Regions Genetic Start site Regulation of gene expression Genetic Variation Promoter Biological Evolution genetic robustness 030104 developmental biology embryonic development genetic variation Adaptive selection expression noise Drosophila Transcription Initiation Site transcription Noise CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | Nature Genetics. 49:550-558 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3791 |
| Popis: | Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution remain unclear. Here we used natural genetic variation across a panel of 81 Drosophila lines to measure changes in transcriptional start site (TSS) usage, identifying thousands of genetic variants affecting transcript levels (strength) or the distribution of TSSs within a promoter (shape). Our results identify promoter shape as a molecular trait that can evolve independently of promoter strength. Broad promoters typically harbor shape-associated variants, with signatures of adaptive selection. Single-cell measurements demonstrate that variants modulating promoter shape often increase expression noise, whereas heteroallelic interactions with other promoter variants alleviate these effects. These results uncover new functional properties of natural promoters and suggest the minimization of expression noise as an important factor in promoter evolution. Fil: Schor, Ignacio Esteban. European Molecular Biology Laboratory Heidelberg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Degner, Jacob F.. European Molecular Biology Laboratory; Alemania Fil: Harnett, Dermot. European Molecular Biology Laboratory; Alemania Fil: Cannavò, Enrico. European Molecular Biology Laboratory; Alemania Fil: Casale, Francesco P.. European Bioinformatics Institute; Reino Unido Fil: Shim, Heejung. Purdue University; Estados Unidos Fil: Garfield, David A.. European Molecular Biology Laboratory; Alemania Fil: Birney, Ewan. European Bioinformatics Institute; Reino Unido Fil: Stephens, Matthew. University of Chicago; Estados Unidos Fil: Stegle, Oliver. European Bioinformatics Institute; Reino Unido Fil: Furlong, Eileen E. M.. European Molecular Biology Laboratory; Alemania |
| Databáze: | OpenAIRE |
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