Abstract:
:Embryonic development is driven by tightly regulated patterns of gene expression, despite extensive genetic variation among individuals. Studies of expression quantitative trait loci (eQTL) indicate that genetic variation frequently alters gene expression in cell-culture models and differentiated tissues. However, the extent and types of genetic variation impacting embryonic gene expression, and their interactions with developmental programs, remain largely unknown. Here we assessed the effect of genetic variation on transcriptional (expression levels) and post-transcriptional (3' RNA processing) regulation across multiple stages of metazoan development, using 80 inbred Drosophila wild isolates, identifying thousands of developmental-stage-specific and shared QTL. Given the small blocks of linkage disequilibrium in Drosophila, we obtain near base-pair resolution, resolving causal mutations in developmental enhancers, validated transcription-factor-binding sites and RNA motifs. This fine-grain mapping uncovered extensive allelic interactions within enhancers that have opposite effects, thereby buffering their impact on enhancer activity. QTL affecting 3' RNA processing identify new functional motifs leading to transcript isoform diversity and changes in the lengths of 3' untranslated regions. These results highlight how developmental stage influences the effects of genetic variation and uncover multiple mechanisms that regulate and buffer expression variation during embryogenesis.
journal_name
Naturejournal_title
Natureauthors
Cannavò E,Koelling N,Harnett D,Garfield D,Casale FP,Ciglar L,Gustafson HE,Viales RR,Marco-Ferreres R,Degner JF,Zhao B,Stegle O,Birney E,Furlong EEdoi
10.1038/nature20802subject
Has Abstractpub_date
2017-01-19 00:00:00pages
402-406issue
7637eissn
0028-0836issn
1476-4687pii
nature20802journal_volume
541pub_type
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