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Role of Ldb1 binding partners Eto2 and cdk9 during stem cells development and erythroid differentiation

Final Activity Report Summary - Ldb1-complexes (Role of Ldb1 binding partners Eto2 and cdk9 during stem cells development and erythroid differentiation)

The emergence of the hematopoietic system, comprising all blood cells, is tightly controlled by a set of highly conserved transcription factors. The way in which these factors regulate blood cells formation, proliferation and differentiation is largely unknown.

The aim of the present work was to analyse the functions of two newly identified key transcription factors, namely Eto2 and Cdk9. A proteomic screen was conducted in the laboratory to identify Eto2 and Cdk9 associated proteins in erythroid cells in order to better understand their functions. This screen showed that Eto2 and Cdk9 could form different sub-complexes, each of them being connected to different chromatin remodelling factors. Relevant data remained unpublished by the time of the project completion.

In combination to this proteomic analysis, a genome-wide mapping of Eto2 binding site was carried out using the chromatin immunoprecipitation sequencing (ChIP-sequencing) technology, which allowed for the identification of the deoxyribonucleic acid (DNA) elements and target genes bound by the different Eto2 complexes. The same experiments were also underway with Cdk9. Furthermore, identical experiments were successfully conducted with other hematopoietic transcription factors connected to Eto2 and Cdk9, such as Ldb1, Tal1 and Gata1.

The collected results shed light on how these transcription factors co-regulated the proliferating capacity of erythroid progenitors. Combining all these results would finally allow us to unravel how transcription factor networks were formed and to control cell fate during hematopoietic tissue development.