Noncoding RNA-nucleated heterochromatin spreading is intrinsically labile and requires accessory elements for epigenetic stability

ELife
R A GreensteinBassem Al-Sady

Abstract

The heterochromatin spreading reaction is a central contributor to the formation of gene-repressive structures, which are re-established with high positional precision, or fidelity, following replication. How the spreading reaction contributes to this fidelity is not clear. To resolve the origins of stable inheritance of repression, we probed the intrinsic character of spreading events in fission yeast using a system that quantitatively describes the spreading reaction in live single cells. We show that spreading triggered by noncoding RNA-nucleated elements is stochastic, multimodal, and fluctuates dynamically across time. This lack of stability correlates with high histone turnover. At the mating type locus, this unstable behavior is restrained by an accessory cis-acting element REIII, which represses histone turnover. Further, REIII safeguards epigenetic memory against environmental perturbations. Our results suggest that the most prevalent type of spreading, driven by noncoding RNA-nucleators, is epigenetically unstable and requires collaboration with accessory elements to achieve high fidelity.

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Citations

Jun 5, 2019·Nature Reviews. Genetics·Xiao Li, Xiang-Dong Fu
Nov 1, 2018·Nature Methods·Sophia M HirschJulie C Canman
May 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Amber R Cutter DiPiazzaShiv I S Grewal
Nov 3, 2021·The FEBS Journal·Chun-Min ShanSongtao Jia

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Methods Mentioned

BETA
FACS
ChIP
flow cytometry
Fluorescence Activated Cell Sorting
Immunoprecipitation
dissect
fluorescence microscopy
environmental stress
PCR
flow

Software Mentioned

Fiji
MATLAB
NIS Elements
FlowJo
critic
HEATMAP
R
FYLM
LEFT
FYLM Critic

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