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

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 repre...

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Autores principales: Al‐Raawi, Diaa, Jones, Rhian, Wijesinghe, Susanne, Halsall, John, Petric, Marija, Roberts, Sally, Hotchin, Neil A, Kanhere, Aditi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356158/
https://www.ncbi.nlm.nih.gov/pubmed/30573669
http://dx.doi.org/10.15252/embj.201798449
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author Al‐Raawi, Diaa
Jones, Rhian
Wijesinghe, Susanne
Halsall, John
Petric, Marija
Roberts, Sally
Hotchin, Neil A
Kanhere, Aditi
author_facet Al‐Raawi, Diaa
Jones, Rhian
Wijesinghe, Susanne
Halsall, John
Petric, Marija
Roberts, Sally
Hotchin, Neil A
Kanhere, Aditi
author_sort Al‐Raawi, Diaa
collection PubMed
description 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.
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spelling pubmed-63561582019-02-07 A novel form of JARID2 is required for differentiation in lineage‐committed cells Al‐Raawi, Diaa Jones, Rhian Wijesinghe, Susanne Halsall, John Petric, Marija Roberts, Sally Hotchin, Neil A Kanhere, Aditi EMBO J Articles 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. John Wiley and Sons Inc. 2018-12-20 2019-02-01 /pmc/articles/PMC6356158/ /pubmed/30573669 http://dx.doi.org/10.15252/embj.201798449 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Al‐Raawi, Diaa
Jones, Rhian
Wijesinghe, Susanne
Halsall, John
Petric, Marija
Roberts, Sally
Hotchin, Neil A
Kanhere, Aditi
A novel form of JARID2 is required for differentiation in lineage‐committed cells
title A novel form of JARID2 is required for differentiation in lineage‐committed cells
title_full A novel form of JARID2 is required for differentiation in lineage‐committed cells
title_fullStr A novel form of JARID2 is required for differentiation in lineage‐committed cells
title_full_unstemmed A novel form of JARID2 is required for differentiation in lineage‐committed cells
title_short A novel form of JARID2 is required for differentiation in lineage‐committed cells
title_sort novel form of jarid2 is required for differentiation in lineage‐committed cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356158/
https://www.ncbi.nlm.nih.gov/pubmed/30573669
http://dx.doi.org/10.15252/embj.201798449
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