Development of gene expression signatures for TLX1 overexpression in human thymus C34+ T-cell progenitors cultured on an OP9-DLL1 feeder layer

ABSTRACT: 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. Thes

ORGANISM(S): Homo sapiens

SUBMITTER: Kaat Durinck 

PROVIDER: E-GEOD-62143 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress