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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...

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Updated: Apr 28, 2026

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Regulatory interactions between RNA and polycomb repressive complex 2.

Catherine Cifuentes-Rojas¹, Alfredo J Hernandez², Kavitha Sarma¹

¹Howard Hughes Medical Institute, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

|June 3, 2014

Summary

This summary is machine-generated.

Polycomb repressive complex 2 (PRC2) uses RNA to target genes. RNA inhibits PRC2 activity until JARID2 binding, revealing a novel regulatory mechanism for gene expression control.

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Area of Science:

Epigenetics
Molecular Biology
Gene Regulation

Background:

Polycomb repressive complex 2 (PRC2) is crucial for gene silencing and implicated in diseases.
Recruitment mechanisms for PRC2 to target genes are not fully understood.
cis-regulatory RNA has been proposed as a key factor in PRC2 localization.

Purpose of the Study:

To biochemically and functionally investigate the interaction between PRC2 and RNA.
To elucidate the role of specific PRC2 subunits in RNA binding and recognition.
To understand how RNA influences PRC2's catalytic activity and chromatin targeting.

Main Methods:

Biochemical assays to measure RNA binding affinities of PRC2 subunits.
Functional studies using the X-inactivation model.
Enzymatic activity assays for PRC2 in the presence of RNA and JARID2.

Main Results:

PRC2 exhibits high discriminatory capabilities in RNA recognition.
EZH2 subunit shows the highest affinity for RNA, with EED modulating this interaction.
RNA binding is essential for targeting but inhibits EZH2's catalytic activity, which is relieved by JARID2.

Conclusions:

RNA acts as a guide for PRC2 to target genes.
JARID2 binding to chromatin-bound PRC2 is necessary to relieve RNA-mediated catalytic inhibition.
This study provides a molecular understanding of RNA-PRC2 interactions at the chromatin interface, impacting gene regulation insights.