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Series GSE117349 Query DataSets for GSE117349
Status Public on Jul 19, 2018
Title Divergence in DNA specificity among paralogous transcription factors contributes to their differential in vivo binding [uPBM_E2f1E2f3E2f]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by array
Summary Members of transcription factor (TF) families, i.e. paralogous TFs, are oftentimes reported to have identical DNA-binding motifs, despite the fact that they perform distinct regulatory functions in the cell. Differential genomic targeting by paralogous TFs is generally assumed to be due to interactions with protein cofactors or the chromatin environment. Contrary to previous assumptions, we find that paralogous TFs have different intrinsic preferences for DNA, not captured by current motif models, and these differences partly explain differential genomic binding and functional specificity. Our finding was possible due to a unique combination of carefully designed high-throughput assays and rigorous computation modeling, integrated into a unified framework called iMADS. We used iMADS to quantity, model, and analyze specificity differences between 11 paralogous TFs from 4 distinct human TF families. Our finding of differential specificity between closely related TFs has important implications for the interpretation of the regulatory effects of non-coding genetic variants.
Overall design Universal protein-binding microarray (PBM) experiments were performed for recombinant, full-length, human transcription factors E2f1, E2f3, and E2f4. Briefly, universal PBMs involved binding of GST-tagged transcription factors to double-stranded 44K Agilent microarrays containing a DNA library designed to cover all possible 10-bp sequences, with every 8-mer occurring in at least 16 different spots on the array. This design allows comprehensive and unbiased characterization of the binding specificity of transcription factors for all possible 8-bp sequences.
Contributor(s) Gordan R
Citation(s) 29605182
Submission date Jul 18, 2018
Last update date Oct 19, 2018
Contact name Raluca Gordan
Organization name Duke University
Department Center for Genomic and Computational Biology
Street address 101 Science Dr, CIEMAS 2179
City Durham
State/province NC
ZIP/Postal code 27708
Country USA
Platforms (1)
GPL23935 Universal PBM 4x44k (Bulyk lab design)
Samples (3)
GSM3291581 E2f1 at 200 nM concentration
GSM3291582 E2f3 at 200 nM concentration
GSM3291583 E2f4 at 200 nM concentration
This SubSeries is part of SuperSeries:
GSE97794 Divergence in DNA specificity among paralogous transcription factors contributes to their differential in vivo binding
BioProject PRJNA481797

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
GSE117349_RAW.tar 8.5 Mb (http)(custom) TAR (of TXT)
Processed data provided as supplementary file

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