Researchers peek into chromosomes’ 3D structure in unprecedented detail

Autor: Amber Dance
Rok vydání: 2020
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 117:25186-25189
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.2017799117
Popis: Clodagh O’Shea will never forget the moment in early 2015 when she peered at the cell’s nucleus in a way no one had ever done before. Using a new technique to visualize three-dimensional (3D) chromosomes as they exist in the active, unadulterated nucleus, O’Shea was able to zoom in on individual nucleosomes where DNA wrapped around organizing proteins, then zoom out to see the entire scraggly mass. “It was just like seeing another planet, this whole new world,” recalls O’Shea, a molecular biologist at the Salk Institute in La Jolla, CA. “You get lost in it.” A technique called ChromEMT reveals the details of chromatin ultrastructure, 3D packing, and organization of DNA. From ref. 1. Reprinted with permission from AAAS. As her initial euphoria faded, O’Shea realized the shapes she saw were wholly unexpected. Based on widely accepted notions about how genetic material organizes in vitro, researchers had anticipated that the DNA strands would be neatly wound into regular fibers of 30, 120, and 300–700 nanometers in diameter. Instead, in the intact nucleus, chromosomes appeared as an amorphous tangle—at least at first glance. “Oh my god, how do we make sense of this?” she wondered. Further analysis revealed that chromatin formed chains of 5–24 nanometers across, winding throughout the nucleus; the chains packed tightly in some spots and more loosely in others (1). That doesn’t mean the standard fibers don’t exist, says O’Shea, but “there are probably more structural possibilities.” Since the 2001 publication of the human genome, researchers have navigated DNA mainly as digital strings of As, Ts, Gs, and Cs. Related research has led to intriguing advances, such as testing for genetic risk factors for disease and precision medicine. But the work hasn’t met expectations when it comes to disease cures, notes Cliff Brangwynne, a chemical and …
Databáze: OpenAIRE