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Characterizing the contrasting roles of JMJD3 and UTX histone demethylases in T cell acute lymphoblastic leukemia [GSKJ4_ChIP-seq]

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we chemically inhibited the H3K27me3 demethylase JMJD3 using the GSKJ4 inhibitor and assayed for genome-wide changes in H3K27me3 and JMJD3 enrichment. This piece of data was further integrated to expression changes using RNA sequencing as well as ChIP-Sequencing analysis of H3K27me3 upon genomic knock-down of JMJD3 and UTX. These results, coupled to genomic analysis of primary samples for the genomic status of the UTX gene in T-ALL, helped us to identify a hitherto unknown role of JMJD3 as an oncogenice facilitator in leukemia whereas UTX seems to play a tumor suppressor role. Histone ChIP: Half to one million cells were treated with micrococcal nuclease (MNASE) to generate mononucleosomal particles and an adaptation of the Upstate ChIP protocol was used.

ORGANISM(S): Homo sapiens

SUBMITTER: Panagiotis Ntziachristos 

PROVIDER: E-GEOD-56693 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified; however, 'epigenetic' drugs are not currently used for T-  ...[more]

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