A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element

Area of Science:

• Developmental Biology
• Epigenetics
• Molecular Biology

Background:

• Polycomb/Trithorax response elements (PRE/TREs) reversibly control gene expression, but the underlying mechanisms remain unclear.
• Noncoding RNAs are increasingly recognized for their roles in gene regulation.

Purpose of the Study:

• To investigate how noncoding transcription from PRE/TREs influences gene silencing and activation.
• To elucidate the role of noncoding RNAs in regulating Polycomb repressive complex 2 (PRC2) activity at PRE/TREs.

Main Methods:

• Utilized Drosophila melanogaster vestigial (vg) PRE/TRE as a model system.
• Analyzed noncoding RNA transcription, PRC2 binding, and chromatin modifications in vitro and in vivo.
• Performed genome-wide analysis of Polycomb-binding sites.

Main Results:

• Switching noncoding transcription direction (forward vs. reverse) at the vg PRE/TRE altered its function between silencing and activation.
• Both forward and reverse noncoding RNAs inhibited PRC2 activity in vitro, but only reverse RNA bound PRC2 in vivo.
• Overexpression of reverse RNA evicted PRC2 and inhibited its activity, suggesting regulated inhibition.

Conclusions:

• Identified a novel class of PRE/TREs that switch function via directional noncoding RNA transcription.
• RNA-PRC2 interactions are differentially regulated in vivo, enabling precise control of gene expression.
• This mechanism of strand switching is potentially widespread across fly and vertebrate genomes.