Mapping Nucleosome Resolution Chromosome Folding in Yeast by Micro-C

Tsung Han S. Hsieh, Assaf Weiner, Bryan Lajoie, Job Dekker, Nir Friedman, Oliver J. Rando*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

431 Scopus citations

Abstract

Summary 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.

Original languageAmerican English
Pages (from-to)108-119
Number of pages12
JournalCell
Volume162
Issue number1
DOIs
StatePublished - 2 Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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