Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements.

TitleTranscriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements.
Publication TypeJournal Article
Year of Publication2015
AuthorsErokhin, M, Elizar'ev, P, Parshikov, A, Schedl, P, Georgiev, P, Chetverina, D
JournalProc Natl Acad Sci U S A
Volume112
Issue48
Pagination14930-5
Date Published2015 Dec 01
ISSN1091-6490
KeywordsAnimals, Chromosomal Proteins, Non-Histone, Drosophila melanogaster, Drosophila Proteins, Epigenesis, Genetic, Polycomb Repressive Complex 1, Response Elements, Transcription, Genetic
Abstract

<p>In Drosophila, Polycomb (PcG) and Trithorax (TrxG) group proteins are assembled on Polycomb response elements (PREs) to maintain tissue and stage-specific patterns of gene expression. Critical to coordinating gene expression with the process of differentiation, the activity of PREs can be switched "on" and "off." When on, the PRE imposes a silenced state on the genes in the same domain that is stably inherited through multiple rounds of cell division. When the PRE is switched off, the domain is in a state permissive for gene expression that can be stably inherited. Previous studies have suggested that a burst of transcription through a PRE sequence displaces PcG proteins and provides a universal mechanism for inducing a heritable switch in PRE activity from on to off; however, the evidence favoring this model is indirect. Here, we have directly tested the transcriptional read-through mechanism. Contrary to previous suggestions, we show that transcription through the PRE is not sufficient for inducing an epigenetic switch in PRE activity. In fact, even high levels of continuous transcription through a PRE fails to dislodge the PcG proteins, nor does it remove repressive histone marks. Our results indicate that other mechanisms involving adjacent DNA regulatory elements must be implicated in heritable switch of PRE activity. </p>

DOI10.1073/pnas.1515276112
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID26504232
PubMed Central IDPMC4672805
Grant ListR01 GM043432 / GM / NIGMS NIH HHS / United States
R01GM043432 / GM / NIGMS NIH HHS / United States