Accession	GSE94732
Status	2018/7/10
Title	Targeting the HBZ Viral Oncoprotein Transcriptional Network in Adult T-cell leukemia/lymphoma (ChIP-Seq)
Organism	Homo sapiens
Experiment type	Genome binding/occupancy profiling by high throughput sequencing
Summary	Adult T-cell Leukemia/Lymphoma (ATLL) is a frequently incurable disease associated with the human lymphotropic virus type I (HTLV-I). The transcription factor HBZ is the only virally encoded gene that is expressed in all ATLL cases, but it is unclear why it may be essential in ATLL and how it might be targeted therapeutically. Here we performed RNA interference screening of ATLL lines and discovered that their proliferation depends on the transcription factors BATF3 and IRF4, which regulate the identity of normal immune cells. These factors, which are highly expressed in ATLL, cooperatively bind and transactivate genes that distinguish ATLL from other T cell malignancies, including BATF3 itself. HBZ binds to an ATLL-specific BATF3 super-enhancer and thereby regulates the expression of BATF3 and its downstream targets, including the oncogene MYC. The BET protein inhibitor JQ1 collapsed the transcriptional network directed by HBZ and BATF3, and was consequently toxic for ATLL lines and patient samples in vitro, and blocked growth of ATLL xenografts. Our study demonstrates that the HTLV-I virus exploits a regulatory module that can potentially be attacked therapeutically with BET protein inhibitors.
Samples	GSM ID Sample info Characteristics Description GSM2481668 KK1 IgG Control cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481669 KK1 IRF4 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481670 ST1 IgG Control cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481671 ST1 IRF4 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481672 ST1 BirA Empty Control - repeat 1 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481673 ST1 BirA BATF3 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481674 KK1 IgG Negative Control cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481675 KK1 BATF3 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481676 ST1 IgG Negative Control cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481677 ST1 BATF3 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481678 KK1 BirA Empty Control - repeat 1 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481679 KK1 BirA HBZ cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481680 ST1 BirA Empty Control - repeat 2 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481681 ST1 BirA HBZ cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481682 KK1 DMSO Treated H3K27ac cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481683 KK1 DMSO Treated BRD4 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481684 KK1 JQ1 Treated H3K27ac cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481685 KK1 JQ1 Treated BRD4 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481686 ST1 DMSO Treated H3K27ac cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481687 ST1 DMSO Treated BRD4 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481688 ST1 JQ1 Treated H3K27ac cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481689 ST1 JQ1 Treated BRD4 cell line:ST1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481690 KK1 BirA Empty Control - repeat 2 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information. GSM2481691 KK1 BirA BATF3 cell line:KK1; disease state:Adult T-cell Leukemia/Lymphoma (ATLL) No additional information.
Platform	GPL18573  GPL23049  : Illumina NextSeq 500 (Homo sapiens);illumina Genome Analyzer IIx (Homo sapiens)
Literature	30057145
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