H3K27ac ChIP-Seq in LOUCY
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Annelynn Wallaert
PROVIDER: E-GEOD-74311 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia.
Wallaert A A Durinck K K Van Loocke W W Van de Walle I I Matthijssens F F Volders P J PJ Avila Cobos F F Rombaut D D Rondou P P Mestdagh P P Vandesompele J J Poppe B B Taghon T T Soulier J J Van Vlierberghe P P Speleman F F
Leukemia 20160422 9
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Project description:H3K27ac ChIP-Seq data of the T-ALL cell line LOUCY was obtained to find active regions in the genome and to correlate that with expression profiling of lncRNAs in the LOUCY cell line.
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Project description:The T-cell leukemia homeobox 1 (TLX1, HOX11) transcription factor is critically involved in the multistep pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanisms by which these T-cell specific oncogenes cooperate during transformation remain to be established. Here, we used an integrative genomics approach to show that the oncogenic properties of TLX1 are mediated by genome-wide interference with the ETS1 and RUNX1 transcription factors. Partial disruption of ETS1 and RUNX1 activity by ectopic TLX1 expression in immature thymocytes drives repression of T-cell specific super-enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 signaling. These phenomena coordinately trigger a TLX1 driven pre-leukemic phenotype in human thymic precursor cells, which corresponds with the in vivo thymic regression observed in murine TLX1 tumor models, and creates a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multistep pathogenesis of TLX1 driven human leukemia. ChIP-sequencing data was generated for TLX1 in the T-ALL cell line ALL-SIL.
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Project description:We analyzed the transcriptional consequences of the BET bromodomain inhibitor JQ1 in the T-ALL cell line LOUCY by microarray analysis. Short-term exposure to a low dose of JQ1 (4h, 250nM) provided insights in the genes whose expression was immediately affected by BET bromodomain inhibition. Significantly downregulated genes upon short-term drug treatment included stem-cell associated genes and putative oncogenes such as BAALC, WT1, MN1, MEF2C, LMO1 and LMO2. Genes associated with the 500 highest ranked enhancer regions in LOUCY, were significantly enriched in genes downregulated after JQ1 treatment.
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