TFBSshape

TFBSshape provides a database and analysis framework for DNA shape features of transcription factor binding sites to support interpretation of transcription factor binding specificity.

Key Features:

• Expanded Database: 2,428 structural profiles covering 1,900 transcription factors across 39 species, incorporating TF collections from JASPAR and UniPROBE.
• Incorporation of Methylation Data: Profiles for unmethylated and methylated DNA derived from in vitro high-throughput EpiSELEX-seq binding assays and in vivo datasets from MeDReaders.
• Enhanced Structural Profiles: Each TFBS entry is annotated with 13 DNA shape features and minor groove electrostatic potential for standard DNA, plus four methylation-specific shape features.
• Alignment and Comparison: Shape-based alignment of TFBSs with capabilities for qualitative and quantitative comparison of structural profiles between datasets.
• DNA Shape-Preserving Mutations: Support for deriving nucleotide mutations in TFBSs that preserve DNA shape for experimental design and hypothesis testing.

Scientific Applications:

• TF binding specificity analysis: Identification of DNA shape features that contribute to transcription factor binding specificity at particular positions within target sequences.
• Methylation effect studies: Evaluation of how cytosine methylation alters DNA structural features relevant to transcription factor binding using EpiSELEX-seq and MeDReaders-derived profiles.
• Mutational design: Design of DNA sequence variants that preserve shape to probe mechanistic aspects of protein–DNA recognition.
• Comparative structural genomics: Cross-species comparison of TFBS structural profiles across the provided 39-species collection.

Methodology:

Database construction integrates TF collections from JASPAR and UniPROBE and datasets from EpiSELEX-seq and MeDReaders; structural profiles are generated and annotated with 13 DNA shape features plus minor groove electrostatic potential for standard DNA and four methylation-specific features; shape-based alignment and qualitative/quantitative profile comparisons are performed.