Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation

Although histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in no...

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Published inNature communications Vol. 6; no. 1; p. 8152
Main Authors Manna, Sugata, Kim, Jong Kyong, Baugé, Catherine, Cam, Margaret, Zhao, Yongmei, Shetty, Jyoti, Vacchio, Melanie S., Castro, Ehydel, Tran, Bao, Tessarollo, Lino, Bosselut, Rémy
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 02.09.2015
Nature Publishing Group
Nature Pub. Group
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Summary:Although histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4 + T-cell precursors. Here we show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1 , encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 was not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty, supporting the conclusion that it requires H3K27Me3 demethylase activity. These findings demonstrate that Jmjd3 and Utx are required for T-cell development, and point to a requirement for their H3K27Me3 demethylase activity in cell differentiation. Histone post-translational modifications such as the trimethylation of histone H3 at lysine 27 (H3K27Me3), affect DNA accessibility and transcription. Here, the authors show that Jmjd3 and Utx, two H3K27Me3 demethylases, are important for regulating the expression of genes involved in terminal thymocyte differentiation.
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PMCID: PMC4569738
Present address: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
Present address: EA4652 Microenvironnement Cellulaire et Pathologies, UFR de médecine, Université de Caen Basse-Normandie, Caen, France
These authors equally contributed to this work
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms9152