Monitoring of switches in heterochromatin-induced silencing shows incomplete establishment and developmental instabilities

Farah Bughio, Gary R. Huckell, Keith A. Maggert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Position effect variegation (PEV) in Drosophila 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.

Original languageEnglish (US)
Pages (from-to)20043-20053
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number40
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • Heterochromatin | position effect variegation | Drosophila gene silencing | epigenetics

ASJC Scopus subject areas

  • General

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