We describe a Hi-C-based method, Micro-C, in which micrococcal nuclease is used 
instead of restriction enzymes to fragment chromatin, enabling nucleosome 
resolution chromosome folding maps. Analysis of Micro-C maps for budding yeast 
reveals abundant self-associating domains similar to those reported in other 
species, but not previously observed in yeast. These structures, far shorter 
than topologically associating domains in mammals, typically encompass one to 
five genes in yeast. Strong boundaries between self-associating domains occur at 
promoters of highly transcribed genes and regions of rapid histone turnover that 
are typically bound by the RSC chromatin-remodeling complex. Investigation of 
chromosome folding in mutants confirms roles for RSC, "gene looping" factor 
Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 
in folding of the yeast genome. This approach provides detailed structural maps 
of a eukaryotic genome, and our findings provide insights into the machinery 
underlying chromosome compaction.