Project description:This SuperSeries is composed of the following subset Series: GSE20544: TAL1 knock down in Jurkat cells GSE20545: TAL1 knock down in human erythroid progenitors Refer to individual Series
Project description:USP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of >200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we show the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 shown accelerated cell growth and validated transcriptional down-regulation of E-protein targets. Our study unveiled the synergistic effect of USP7 haploinsufficiency with aberrant TAL1 activation on T-ALL, implicating USP7 as a haploinsufficient tumor suppressor in T-ALL.
Project description:We have mapped the binding sites for the five key regulators GATA1, GATA2, RUNX1, FLI1 and TAL1/SCL in primary human megakaryocytes. Statistical analysis identified subsets of enriched as well as depleted combinatorial binding patterns. In particular simultaneous binding by all 5 factors was highly enriched and occurred in the vicinity of many genes known to be involved in blood and megakaryocyte development. Knock down in zebrafish of 8 of these genes with no previously known role in hematopoiesis, revealed all to be essential for thrombocyte and/or erythroid development. Combinatorial analysis of multi-factor ChIP-Seq datasets coupled with a high-throughput in vivo screen therefore offers a powerful strategy to identify novel essential regulators of complex mammalian differentiation processes. 5 transcription factors and rabbit-IgG in megakaryocytes.
Project description:Analyses of the consequences of up- and down-regulating SCL/TAL1 in human enriched hematopoietic stem progenitor cells (HSPCs). We used microarrays to detail the global gene expression program of human cord blood HSPCs (CD34+CD38-lowCD34RA-CD90+) in which SCL/TAL1 expression is either up- or down-regulated.