Twisting chromatin in stem cells.

How transcriptional output is orchestrated in mammalian genomes is an area of intense research. The structural organization within the nucleus and the physical association between regulatory elements are considered critical components in this regulation. Recent work published in Nature (de Wit et al, 2013) applied the Circular Chromosome Conformation Capture (4C) method at high resolution in pluripotent stem cells (PSCs), revealing that PSCs uniquely shape their genome around binding sites for pluripotency factors. Many regulatory elements are located distal to regions of active transcription, but looping of DNA can juxtapose these regulatory regions with gene promoters (Dekker et al, 2013). The extent to which DNA elements display physical proximity during development and disease as well as the functional consequences of these three-dimensional (3D) chromosomal associations are poorly understood. Historically speaking, looping of DNA fibres was originally observed in bacteria and subsequently in mammalian cells, where it was proposed to serve a functional role (Splinter and de Laat, 2011). Microscopybased methods were essential for characterizing the first looping interactions in mammalian cells, demonstrating that delineated territories are occupied by particular chromosomes in interphase nuclei (Dekker et al, 2013).