Trac-looping measures genome structure and chromatin accessibility

Interaction between different chromatin regions plays critical roles in genome organization and regulation of transcription. Existing technologies of analyzing genome-wide chromatin interactions rely on in vitro proximity-based ligation of interacting chromatin fragments and thus are prone to potential artifacts. We now report a novel technique, Transposase-mediated Analysis of Chromatin loops (TrAC-loop), for detection of genome-wide chromatin interactions between regulatory regions. With this technique, a bivalent oligonucleotide linker is inserted between two interacting chromatin regions such that the distant interacting chromatin regions can be directly amplified by PCR and thus avoids the prior chromatin fragmentation and subsequent error-prone re-ligation steps. TrAC-loop selectively targets accessible regions, which effectively reduces the sequencing cost for detecting promoter-enhancer interactions at high resolution. Application of TrAC-loop to human CD4+ T cells reveals a substantial reorganization of enhancer-promoter interaction associated with changes in gene expression upon TCR stimulation. Examination of enhancer-promoter interaction associated with changes in gene expression upon TCR stimulation.