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A De Novo Shape Motif Discovery Algorithm Reveals Preferences of Transcription Factors for DNA Shape Beyond Sequence Motifs.

Md Abul Hassan Samee | Benoit G Bruneau | Katherine S Pollard
Cell systems | 2019

DNA shape adds specificity to sequence motifs but has not been explored systematically outside this context. We hypothesized that DNA-binding proteins (DBPs) preferentially occupy DNA with specific structures ("shape motifs") regardless of whether or not these correspond to high information content sequence motifs. We present ShapeMF, a Gibbs sampling algorithm that identifies de novo shape motifs. Using binding data from hundreds of in vivo and in vitro experiments, we show that most DBPs have shape motifs and can occupy these in the absence of sequence motifs. This "shape-only binding" is common for many DBPs and in regions co-bound by multiple DBPs. When shape and sequence motifs co-occur, they can be overlapping, flanking, or separated by consistent spacing. Finally, DBPs within the same protein family have different shape motifs, explaining their distinct genome-wide occupancy despite having similar sequence motifs. These results suggest that shape motifs not only complement sequence motifs but also facilitate recognition of DNA beyond conventionally defined sequence motifs.

Pubmed ID: 30660610

Research resources used in this publication

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Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL098179
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL131003
  • Agency: NHLBI NIH HHS, United States
    Id: UM1 HL098179

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ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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bwtool (tool)

RRID:SCR_003035

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RRID:SCR_007393

Curated protein-protein and genetic interaction repository of raw protein and genetic interactions from major model organism species, with data compiled through comprehensive curation efforts.

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