Building accurate sequence-to-affinity models from high-throughput in vitro protein-DNA binding data using FeatureREDUCE.

Transcription factors are crucial regulators of gene expression. Accurate quantitative definition of their intrinsic DNA binding preferences is critical to understanding their biological function. High-throughput in vitro technology has recently been used to deeply probe the DNA binding specificity of hundreds of eukaryotic transcription factors, yet algorithms for analyzing such data have not yet fully matured.

SELEX-seq: a method for characterizing the complete repertoire of binding site preferences for transcription factor complexes.

The closely related members of the Hox family of homeodomain transcription factors have similar DNA-binding preferences as monomers, yet carry out distinct functions in vivo. Transcription factors often bind DNA as multiprotein complexes, raising the possibility that complex formation might modify their DNA-binding specificities. To test this hypothesis we developed a new experimental and computational platform, termed SELEX-seq, to characterize DNA-binding specificities of Hox-based multiprotein complexes.

Probing DNA shape and methylation state on a genomic scale with DNase I.

DNA binding proteins find their cognate sequences within genomic DNA through recognition of specific chemical and structural features. Here we demonstrate that high-resolution DNase I cleavage profiles can provide detailed information about the shape and chemical modification status of genomic DNA. Analyzing millions of DNA backbone hydrolysis events on naked genomic DNA, we show that the intrinsic rate of cleavage by DNase I closely tracks the width of the minor groove.

Evaluation of methods for modeling transcription factor sequence specificity.

Genomic analyses often involve scanning for potential transcription factor (TF) binding sites using models of the sequence specificity of DNA binding proteins. Many approaches have been developed to model and learn a protein's DNA-binding specificity, but these methods have not been systematically compared. Here we applied 26 such approaches to in vitro protein binding microarray data for 66 mouse TFs belonging to various families.

TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements.

TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS.