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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Impact of Jmjd3 and Utx histone demethylases on Histone H3 lysine 27 trimethylation (H3K27Me3) in mature CD4 SP thymocytes

ABSTRACT: While 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. 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. Floxed alleles of the genes encoding Utx and Jmjd3 (Kdm6a and Kdm6b, respectively) were deleted in double positive (DP) thymocytes carrying a CD4 Cre transgene. Genome-wide H3K27Me3 ChipSeq was performed on (i) pre-selection (CD69lo) DP thymocytes from wild-type mice carrying an endogenous polyclonal TCR repertoire, (ii) mature (TCRhi CD24lo) CD4 SP thymocytes from wild type (Wt), Jmjd3KO, UtxKO and dKO mice carrying an endogenous polyclonal TCR repertoire and (iii) mature (Va2hi CD24lo) CD4 SP thymocytes from wild type and dKO mice carrying the OTII TCR transgene.

ORGANISM(S): Mus musculus

SUBMITTER: Margaret Cam

PROVIDER: E-GEOD-70795 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiling in mature OT-II TCR transgenic CD4 SP thymocytes, either Jmjd3- and Utx-deficient or -sufficient.

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