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JmjC Family of Histone Demethylases Form Nuclear Condensates

The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play ro...

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Autores principales: Vicioso-Mantis, Marta, Aguirre, Samuel, Martínez-Balbás, Marian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319511/
https://www.ncbi.nlm.nih.gov/pubmed/35887017
http://dx.doi.org/10.3390/ijms23147664
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author Vicioso-Mantis, Marta
Aguirre, Samuel
Martínez-Balbás, Marian A.
author_facet Vicioso-Mantis, Marta
Aguirre, Samuel
Martínez-Balbás, Marian A.
author_sort Vicioso-Mantis, Marta
collection PubMed
description The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low-complexity domains and intrinsically disordered regions (IDR), which in some cases reached 70% of the protein. Our data revealed that plant homeodomain finger protein (PHF2), KDM2A, and KDM4B cluster by phase separation. Moreover, our molecular analysis implies that PHF2 IDR contributes to transcription regulation. These data suggest that clustering via phase separation is a common feature that JMJC-KDMs utilize to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus.
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spelling pubmed-93195112022-07-27 JmjC Family of Histone Demethylases Form Nuclear Condensates Vicioso-Mantis, Marta Aguirre, Samuel Martínez-Balbás, Marian A. Int J Mol Sci Article The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low-complexity domains and intrinsically disordered regions (IDR), which in some cases reached 70% of the protein. Our data revealed that plant homeodomain finger protein (PHF2), KDM2A, and KDM4B cluster by phase separation. Moreover, our molecular analysis implies that PHF2 IDR contributes to transcription regulation. These data suggest that clustering via phase separation is a common feature that JMJC-KDMs utilize to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus. MDPI 2022-07-11 /pmc/articles/PMC9319511/ /pubmed/35887017 http://dx.doi.org/10.3390/ijms23147664 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vicioso-Mantis, Marta
Aguirre, Samuel
Martínez-Balbás, Marian A.
JmjC Family of Histone Demethylases Form Nuclear Condensates
title JmjC Family of Histone Demethylases Form Nuclear Condensates
title_full JmjC Family of Histone Demethylases Form Nuclear Condensates
title_fullStr JmjC Family of Histone Demethylases Form Nuclear Condensates
title_full_unstemmed JmjC Family of Histone Demethylases Form Nuclear Condensates
title_short JmjC Family of Histone Demethylases Form Nuclear Condensates
title_sort jmjc family of histone demethylases form nuclear condensates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319511/
https://www.ncbi.nlm.nih.gov/pubmed/35887017
http://dx.doi.org/10.3390/ijms23147664
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