Autoregulation of JARID2 through PRC2 interaction with its antisense ncRNA
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Research Notes Open Access
RESEARCH NOTE
Autoregulation of JARID2 through PRC2 interaction with its antisense ncRNA Diaa Al‑Raawi1,2 and Aditi Kanhere2,3*
Abstract Objective: JARID2 is a member of chromatin-modifying Polycomb Repressive Complex-2 or PRC2. It plays a role in recruiting PRC2 to developmental genes and regulating its activity. JARID2 along with PRC2 is indispensable for nor‑ mal development. However, it remains unclear how JARID2 expression itself is regulated. Recently a number of nonprotein-coding RNAs or ncRNAs are shown to regulate transcription. An antisense ncRNA, JARID2-AS1, is expressed from the first intron of JARID2 isoform-1 but its role in regulation of JARID2 expression has not been investigated. The objective of this study was to explore the role of JARID2-AS1 in regulating JARID2 and consequently PRC2. Results: We found that JARID2-AS1 is localised in the nucleus and shows anti-correlated expression pattern to that of JARID2 isoform-1 mRNA. More interestingly, data mining approach strongly indicates that JARID2-AS1 binds to PRC2. These are important observations that provide insights into transcriptional regulation of JARID2, especially because they indicate that JARID2-AS1 by interacting and probably recruiting PRC2 participates in an auto-regulatory loop that controls levels of JARID2. This holds importance in regulation of developmental and differentiation processes. How‑ ever, to support this hypothesis, further in-depth studies are needed which can verify JARID2-AS1-PRC2 interactions. Keywords: Polycomb repressive complex-2, JARID2, JARID2-AS1, Antisense ncRNA, Autoregulatory loop Introduction Polycomb group (PcG) proteins are highly conserved transcriptional repressive regulators required for maintenance of cell identity during normal metazoan development [1, 2]. They mediate the epigenetic gene silencing by catalysing repressive histone modifications. PcG proteins form two major complexes, polycomb repressive complex-1 (PRC1) and -2 (PRC2). PRC2 consists of four core proteins, SUZ12, EED, RbAp46/48 and the catalytic subunit EZH2. PRC2 catalyses mono-, di- and trimethylation of histone H3 at lysine 27 (H3K27me3) [3, 4]. In mammalian cells, it is not yet completely clear how PRC2 is recruited to its sites of action. Multiple proteomic and genetics studies have revealed that additional proteins *Correspondence: [email protected] 3 Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, United Kingdom Full list of author information is available at the end of the article
like JARID2, interact with PRC2, forming different subclasses of PRC2 complex such as PRC2.1 and PRC2.2 [1, 5–18]. JARID2 is important for PRC2 function as it contributes to recruitment of PRC2 to chromatin and modulating enzymatic activity through its N-terminal region [1]. The N-terminal region of JARID2 comprises of a nucleosomal binding domain and a RNA binding domain, which together play a role in PRC2 recruitment to genomic DNA [19–21]. JARID2’s post-
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