A novel form of JARID2 is required for differentiation in lineage-committed cells

Polycomb repressive complex‐2 (PRC 2) is a group of proteins that play an important role during development and in cell differentiation. PRC 2 is a histone‐modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID 2 is a co‐factor of PRC 2 and is important for targeting PRC 2 to chromatin. Here, we show that, unlike in embryonic stem cells, in lineage‐committed human cells, including human epidermal keratinocytes, JARID 2 predominantly exists as a novel low molecular weight form, which lacks the N‐terminal PRC 2‐interacting domain (ΔN‐JARID 2). We show that ΔN‐JARID 2 is a cleaved product of full‐length JARID 2 spanning the C‐terminal conserved jumonji domains. JARID 2 knockout in keratinocytes results in up‐regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID 2‐null keratinocytes can be rescued by expression of ΔN‐JARID 2 suggesting that, in contrast to PRC 2, ΔN‐JARID 2 promotes activation of differentiation genes. We propose that a switch from expression of full‐length JARID 2 to ΔN‐JARID 2 is important for the up‐regulation differentiation genes

Autoregulation of JARID2 through PRC2 interaction with its antisense ncRNA

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 normal development. However, it remains unclear how JARID2 expression itself is regulated. Recently a number of non-protein-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. However, to support this hypothesis, further in-depth studies are needed which can verify JARID2-AS1-PRC2 interactions