Unknown,Transcriptomics,Genomics,Proteomics

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Differential genomic targeting of the transcription factor TAL1 in alternate hematopoietic lineages


ABSTRACT: TAL1/SCL is a master regulator of hematopoiesis whose expression promotes opposite outcomes depending on the cell type - differentiation in the erythroid lineage or oncogenesis in the T-cell lineage. Here we used a combination of ChIP-sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukemic T-cells. Analysis of the genome-wide binding properties of TAL1 in these two hematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. Our study shows limited overlap in the TAL1 binding profile between the two cell types with an unexpected preference for ETS and RUNX motifs adjacent to E-boxes in the T-cell lineage. Furthermore we show that TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required to target TAL1 to genes that modulate T-cell differentiation. Thus, our findings highlight a critical role of the cellular environment in modulating transcription factor binding, and provide insight into the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in the T-cell lineage. Examine TAL1/SCL binding sites in two different cell lineages (i.e. primary human pro-erythroblasts and the Jurkat T-ALL cell line). These records represent the ChIP-seq part of the study. The gene expresssion part is available at GSE20546.

ORGANISM(S): Homo sapiens

SUBMITTER: Zizhen yao 

PROVIDER: E-GEOD-25000 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential genomic targeting of the transcription factor TAL1 in alternate haematopoietic lineages.

Palii Carmen G CG   Perez-Iratxeta Carolina C   Yao Zizhen Z   Cao Yi Y   Dai Fengtao F   Davison Jerry J   Atkins Harold H   Allan David D   Dilworth F Jeffrey FJ   Gentleman Robert R   Tapscott Stephen J SJ   Brand Marjorie M  

The EMBO journal 20101221 3


TAL1/SCL is a master regulator of haematopoiesis whose expression promotes opposite outcomes depending on the cell type: differentiation in the erythroid lineage or oncogenesis in the T-cell lineage. Here, we used a combination of ChIP sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukaemic T cells. Analysis of the genome-wide binding properties of TAL1 in these two haematopoietic lineages revealed new insight into the mechanism by which transcr  ...[more]

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