Journal
EMBO JOURNAL
Volume 38, Issue 3, Pages -Publisher
WILEY
DOI: 10.15252/embj.201798449
Keywords
cell differentiation; JARID2; N-terminal domain; polycomb; proteolytic cleavage
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Funding
- SSfH fellowship from University of Birmingham
- IDB funding
- Wellcome Trust ISSF grant
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Polycomb repressive complex-2 (PRC2) is a group of proteins that play an important role during development and in cell differentiation. PRC2 is a histone-modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co-factor of PRC2 and is important for targeting PRC2 to chromatin. Here, we show that, unlike in embryonic stem cells, in lineage-committed human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N-terminal PRC2-interacting domain (Delta N-JARID2). We show that Delta N-JARID2 is a cleaved product of full-length JARID2 spanning the C-terminal conserved jumonji domains. JARID2 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 JARID2-null keratinocytes can be rescued by expression of Delta N-JARID2 suggesting that, in contrast to PRC2, Delta N-JARID2 promotes activation of differentiation genes. We propose that a switch from expression of full-length JARID2 to Delta N-JARID2 is important for the up-regulation differentiation genes.
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