Subtypes of associated protein-DNA (Transcription Factor-Transcription Factor Binding Site) patterns.
In protein-DNA interactions, particularly transcription factor (TF) and transcription factor binding site (TFBS) bindings, associated residue variations form patterns denoted as subtypes. Subtypes may lead to changed binding preferences, distinguish conserved from flexible binding residues and reveal novel binding mechanisms. However, subtypes must be studied in the context of core bindings. While solving 3D structures would require huge experimental efforts, recent sequence-based associated TF-TFBS pattern discovery has shown to be promising, upon which a large-scale subtype study is possible and desirable. In this article, we investigate residue-varying subtypes based on associated TF-TFBS patterns. By re-categorizing the patterns with respect to varying TF amino acids, statistically significant (P values ≤ 0.005) subtypes leading to varying TFBS patterns are discovered without using TF family or domain annotations. Resultant subtypes have various biological meanings. The subtypes reflect familial and functional properties and exhibit changed binding preferences supported by 3D structures. Conserved residues critical for maintaining TF-TFBS bindings are revealed by analyzing the subtypes. In-depth analysis on the subtype pair PKVVIL-CACGTG versus PKVEIL-CAGCTG shows the V/E variation is indicative for distinguishing Myc from MRF families. Discovered from sequences only, the TF-TFBS subtypes are informative and promising for more biological findings, complementing and extending recent one-sided subtype and familial studies with comprehensive evidence.
Department of Computer Science & Engineering, The Chinese University of Hong Kong, Shatin, N T, Hong Kong. tmchan@cse.cuhk.edu.hk
Tak-Ming
TM
Chan
Kwong-Sak
KS
Leung
Kin-Hong
KH
Lee
Man-Hon
MH
Wong
Terrence Chi-Kong
TC
Lau
Stephen Kwok-Wing
SK
Tsui
D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D008958:Models, Molecular; D059372:Nucleotide Motifs; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism
D014157:Transcription Factors; D004247:DNA