Interactions between DNA and transcription factors (TFs) guide cellular function 
and development, yet the complexities of gene regulation are still far from 
being understood. Such understanding is limited by a paucity of techniques with 
which to probe DNA-protein interactions. We have devised magnetic protein 
immobilization on enhancer DNA (MagPIE), a simple, rapid, multi-parametric assay 
using flow cytometric immunofluorescence to reveal interactions among TFs, 
chromatin structure and DNA. In MagPIE, synthesized DNA is bound to magnetic 
beads, which are then incubated with nuclear lysate, permitting 
sequence-specific binding by TFs, histones and methylation by native lysate 
factors that can be optionally inhibited with small molecules. Lysate 
protein-DNA binding is monitored by flow cytometric immunofluorescence, which 
allows for accurate comparative measurement of TF-DNA affinity. Combinatorial 
fluorescent staining allows simultaneous analysis of sequence-specific TF-DNA 
interaction and chromatin modification. MagPIE provides a simple and robust 
method to analyze complex epigenetic interactions in vitro.