Microfluidics-Based Chromosome Conformation Capture (3C) Technology for Examining Chromatin Organization with a Low Quantity of Cells.

Detecting three-dimensional (3D) genome organization in the form of physical interactions between various genomic loci is of great importance for understanding transcriptional regulations and cellular fate. Chromosome Conformation Capture (3C) method is the gold standard for examining chromatin organization, but usually requires a large number of cells (>107). This hinders studies of scarce tissue samples from animals and patients using the method. Here we developed a microfluidics-based approach for examining chromosome conformation by 3C technology. Critical 3C steps, such as digestion and religation of BAC DNA and cross-linked chromatin, were implemented on a microfluidic chip using a low quantity of cells (<104). Using this technology, we analyzed the chromatin looping interactions in the human β-globin. We envision that our method will provide a powerful tool for low-input analysis of chromosome conformation and epigenetic regulations.