Abstract:
: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.
journal_name
Cell Systjournal_title
Cell systemsauthors
Samee MAH,Bruneau BG,Pollard KSdoi
10.1016/j.cels.2018.12.001subject
Has Abstractpub_date
2019-01-23 00:00:00pages
27-42.e6issue
1eissn
2405-4712issn
2405-4720pii
S2405-4712(18)30475-7journal_volume
8pub_type
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