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Series GSE211655 Query DataSets for GSE211655
Status Public on Dec 15, 2022
Title Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila random variant STARR-seq]
Organism Drosophila melanogaster
Experiment type Other
Summary The information about when and where each gene is to be expressed is mainly encoded in the DNA sequence of enhancers, sequence elements that comprise binding sites (motifs) for different transcription factors (TFs). Most of the research on enhancer sequences has been focused on TF motif presence, while the enhancer syntax, i.e. the flexibility of important motif positions and how the sequence context modulates the activity of TF motifs, remain poorly understood. Here, we explore the rules of enhancer syntax by a two-pronged approach in Drosophila melanogaster S2 cells: we (1) replace important motifs by an exhaustive set of all possible 65,536 eight-nucleotide-long random sequences and (2) paste eight important TF motif types into 763 motif positions within 496 enhancers. These complementary strategies reveal that enhancers display constrained sequence flexibility and the context-specific modulation of motif function. Important motifs can be functionally replaced by hundreds of sequences constituting several distinct motif types, but only a fraction of all possible sequences and motif types restore enhancer activity. Moreover, TF motifs contribute with different intrinsic strengths that are strongly modulated by the enhancer sequence context (the flanking sequence, presence and diversity of other motif types, and distance between motifs), such that not all motif types can work in all positions. Constrained sequence flexibility and the context-specific modulation of motif function are also hallmarks of human enhancers and TF motifs, as we demonstrate experimentally. Overall, these two general principles of enhancer sequences are important to understand and predict enhancer function during development, evolution and in disease.
 
Overall design UMI-STARR-seq was performed in S2 cells using a enhancer libraries where we replace important motifs by an exhaustive set of all possible 65,536 eight-nucleotide-long random sequences. All experiments were performed in 2 biological replicates.
 
Contributor(s) Reiter F, de Almeida BP, Stark A
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Submission date Aug 19, 2022
Last update date Dec 15, 2022
Contact name Bernardo P de Almeida
E-mail(s) bernardo.almeida@imp.ac.at
Organization name Research Institute of Molecular Pathology (IMP)
Lab Stark Lab
Street address Campus-Vienna-Biocenter 1
City Wien
ZIP/Postal code 1030
Country Austria
 
Platforms (1)
GPL25244 Illumina NovaSeq 6000 (Drosophila melanogaster)
Samples (8)
GSM6482114 ced-6 enhancer libraries rep1 input
GSM6482115 ced-6 enhancer libraries rep2 input
GSM6482116 ced-6 enhancer libraries rep1 STARR-seq
This SubSeries is part of SuperSeries:
GSE211659 Enhancers display sequence flexibility constrained by transcription factor motif syntax
Relations
BioProject PRJNA871263

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE211655_Table_enhancer_variant_counts_and_enrichment.txt.gz 22.9 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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