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

Diaa Al-Raawi, Rhian Jones, Susanne Wijesinghe, John Halsall, Marija Petric, Sally Roberts, Neil Hotchin, Aditi Kanhere

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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Abstract

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 (ΔN-JARID2). We show that ΔN-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 ΔN-JARID2 suggesting that, in contrast to PRC2, ΔN-JARID2 promotes activation of differentiation genes. We propose that a switch from expression of full-length JARID2 to ΔN-JARID2 is important for the up-regulation differentiation genes.

Original languageEnglish
Article numbere98449
Number of pages13
JournalThe EMBO journal
Volume38
Issue number3
Early online date20 Dec 2018
DOIs
Publication statusPublished - 1 Feb 2019

Bibliographical note

© 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords

  • JARID2
  • N‐terminal domain
  • cell differentiation
  • polycomb
  • proteolytic cleavage

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