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Cell. 2017 Dec 14;171(7):1508-1519.e13. doi: 10.1016/j.cell.2017.10.043. Epub 2017 Nov 30.

Resetting the Yeast Epigenome with Human Nucleosomes.

Author information

1
Institute for Systems Genetics, Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA. Electronic address: davemtruong@gmail.com.
2
Institute for Systems Genetics, Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA. Electronic address: jef.boeke@nyumc.org.

Abstract

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.

KEYWORDS:

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

PMID:
29198523
PMCID:
PMC5732057
DOI:
10.1016/j.cell.2017.10.043
[Indexed for MEDLINE]
Free PMC Article

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