Single-molecule regulatory architectures captured by chromatin fiber sequencing

Primary architecture of chromatin fibers The organization of chromosomal DNA, including the positioning of nucleosomes and nucleosome-free regions harboring regulatory proteins along single chromatin fibers, is fundamental to genome function. However, most sequencing methods cannot elucidate this organization at the nucleotide level. Stergachis et al. present an approach, Fiber-seq, that maps chromatin fibers onto the underlying DNA template using methyltransferases to create a kind of stencil in fly and human cells. This method identifies chromatin structure at nearly a single-molecule level and can monitor the position of nucleosomes. Using Fiber-seq, the authors identify how regulatory DNA activation is related to nucleosome positioning and DNA variation. Science , this issue p. 1449