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

Al-Raawi, D, Jones, R, Wijesinghe, S, Halsall, J, Petric, M, Roberts, S, Hotchin, NA and Kanhere, A
(2019) A novel form of JARID2 is required for differentiation in lineage-committed cells. The EMBO Journal, 38 (3). e98449-.

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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.

Item Type: Article
Uncontrolled Keywords: cell differentiation, JARID2, N-terminal domain, polycomb, proteolytic cleavage
Depositing User: Symplectic Admin
Date Deposited: 31 Oct 2019 15:19
Last Modified: 19 Jan 2023 00:21
DOI: 10.15252/embj.201798449
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3060105