Monitoring of Switches in Heterochromatin-induced Silencing Shows Incomplete Establishment and Developmental Instabilities

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Sep 19

PMID 31527269

Citations 4

Authors

Farah Bughio

Gary R Huckell

Keith A Maggert

Affiliations

Soon will be listed here.

Abstract

Position effect variegation (PEV) in results from new juxtapositions of euchromatic and heterochromatic chromosomal regions, and manifests as striking bimodal patterns of gene expression. The semirandom patterns of PEV, reflecting clonal relationships between cells, have been interpreted as gene-expression states that are set in development and thereafter maintained without change through subsequent cell divisions. The rate of instability of PEV is almost entirely unexplored beyond the final expression of the modified gene; thus the origin of the expressivity and patterns of PEV remain unexplained. Many properties of PEV are not predicted from currently accepted biochemical and theoretical models. In this work we investigate the time at which expressivity of silencing is set, and find that it is determined before heterochromatin exists. We employ a mathematical simulation and a corroborating experimental approach to monitor switching (i.e., gains and losses of silencing) through development. In contrast to current views, we find that gene silencing is incompletely set early in embryogenesis, but nevertheless is repeatedly lost and gained in individual cells throughout development. Our data support an alternative to locus-specific "epigenetic" silencing at variegating gene promoters that more fully accounts for the final patterns of PEV.

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