Resetting the Yeast Epigenome with Human Nucleosomes

David M. Truong, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Humans and yeast are separated by a billion years of evolution, yet their conserved histones retain central roles in gene regulation. Here, we “reset” yeast to use core human nucleosomes in lieu of their own (a rare event taking 20 days), which initially only worked with variant H3.1. The cells adapt by acquiring suppressor mutations in cell-division genes or by acquiring certain aneuploid states. Converting five histone residues to their yeast counterparts restored robust growth. We reveal that humanized nucleosomes are positioned according to endogenous yeast DNA sequence and chromatin-remodeling network, as judged by a yeast-like nucleosome repeat length. However, human nucleosomes have higher DNA occupancy, globally reduce RNA content, and slow adaptation to new conditions by delaying chromatin remodeling. These humanized yeasts (including H3.3) pose fundamental new questions about how chromatin is linked to many cell processes and provide a platform to study histone variants via yeast epigenome reprogramming. Yeast can survive with human histones, providing insight into the regulation of nucleosome positioning and remodeling.

Original languageEnglish (US)
Pages (from-to)1508-1519.e13
Issue number7
StatePublished - Dec 14 2017
Externally publishedYes


  • chromatin
  • genomics
  • histone
  • histones
  • humanized
  • synthetic biology
  • systems biology

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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