Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements.
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.
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia;
Maksim
M
Erokhin
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia;
Pavel
P
Elizar'ev
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia;
Aleksander
A
Parshikov
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia; Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Paul
P
Schedl
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia; georgiev_p@mail.ru daria.chetverina@gmail.com.
Pavel
P
Georgiev
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia; georgiev_p@mail.ru daria.chetverina@gmail.com.
Darya
D
Chetverina
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D044127:Epigenesis, Genetic / Q000502:physiology*; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C066770:Pc protein, Drosophila; C512571:trx protein, Drosophila; D063150:Polycomb Repressive Complex 1
Polycomb; Trithorax; bithorax; chromatin silencing; intergenic transcription