We present Micro-C XL, an improved method for analysis of chromosome folding at 
mononucleosome resolution. Using long crosslinkers and isolation of insoluble 
chromatin, Micro-C XL increases signal-to-noise ratio. Micro-C XL maps of 
budding and fission yeast genomes capture both short-range chromosome fiber 
features such as chromosomally interacting domains and higher order features 
such as centromere clustering. Micro-C XL provides a single assay to interrogate 
chromosome folding at length scales from the nucleosome to the full genome.