Dataset Information

Interactome of the TCF3-HLF fusion protein

ABSTRACT: Oncogenic chimeric transcription factors are central drivers in cancer. To understand how the TCF3-HLF fusion protein rewires the transcriptional landscape in t(17;19) positive leukemia, functional genetic and proteomic experiments were conducted. In this dataset, the protein-protein interactions of the endogenous TCF3-HLF complex were characterized by AP-MS.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Fabian Frommelt

LAB HEAD: Jean-Pierre Bourquin

PROVIDER: PXD014992 | Pride | 2020-08-05

REPOSITORIES: Pride

ACCESS DATA

Publications

The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability.

Huang Yun Y Mouttet Brice B Warnatz Hans-Jörg HJ Risch Thomas T Rietmann Fabian F Frommelt Fabian F Ngo Quy A QA Dobay Maria Pamela MP Marovca Blerim B Jenni Silvia S Tsai Yi-Chien YC Matzk Sören S Amstislavskiy Vyacheslav V Schrappe Martin M Stanulla Martin M Gstaiger Matthias M Bornhauser Beat B Yaspo Marie-Laure ML Bourquin Jean-Pierre JP

Cancer cell 20191114 6

The chimeric transcription factor TCF3-HLF defines an incurable acute lymphoblastic leukemia subtype. Here we decipher the regulome of endogenous TCF3-HLF and dissect its essential transcriptional components and targets by functional genomics. We demonstrate that TCF3-HLF recruits HLF binding sites at hematopoietic stem cell/myeloid lineage associated (super-) enhancers to drive lineage identity and self-renewal. Among direct targets, hijacking an HLF binding site in a MYC enhancer cluster by TC ...[more]

PMID: 31735627

Similar Datasets

Project description:Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is are often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na2CrO4), a well known human respiratory carcinogen that induces a wide spectrum of DNA damage, in the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate. Notably, PTP inhibition abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after PTP inhibition was predominantly due to a bypass of cell cycle arrest and was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by PTP inhibition, was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in the Cr(VI)-induced expression of cell cycle promoting genes. Importantly, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability, via bypass of cell cycle checkpoints. Experiment Overall Design: Experimental factor was chemical treatment type (3 of them) Experiment Overall Design: (1) No: HLF 1-1, HLF 1-2, HLF 1-3, HLF 1-4 Experiment Overall Design: (2) 1uM Cr(VI): HLF 3-1, HLF 3-2, HLF 3-3, HLF 3-4 Experiment Overall Design: (3) 10uM SOV + 1uM Cr(VI): HLF 4-1, HLF 4-2, HLF 4-3, HLF 4-4 Experiment Overall Design: Biological replicates: 4 different RNA extractions from 4 different cell cultures=quadruplicate per chemical treatment type

Dataset Information

Interactome of the TCF3-HLF fusion protein

Publications

The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure