Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation.

Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here, we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells.

Widespread perturbation of ETS factor binding sites in cancer.

Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types.

Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT.

A proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e.

CASCADE: high-throughput characterization of regulatory complex binding altered by non-coding variants.

Non-coding DNA variants (NCVs) impact gene expression by altering binding sites for regulatory complexes. New high-throughput methods are needed to characterize the impact of NCVs on regulatory complexes. We developed CASCADE (Customizable Approach to Survey Complex Assembly at DNA Elements), an array-based high-throughput method to profile cofactor (COF) recruitment.

High-Throughput Analysis of the Cell and DNA Site-Specific Binding of Native NF-κB Dimers Using Nuclear Extract Protein-Binding Microarrays (NextPBMs).

Nuclear factor-kappa B (NF-κB) transcription factors coordinate gene expression in response to a broad array of cellular signals. In vertebrates, there are five NF-κB proteins (c-Rel, RelA/p65, RelB, p50, and p52) that can form various dimeric combinations exhibiting both common and dimer-specific DNA-binding specificity. In this chapter, we describe the use of the nuclear extract protein-binding microarray (nextPBM), a high-throughput method to characterize the DNA binding of transcription factors present in cell nuclear extracts.