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- W2038238077 abstract "The RUNX1 transcription factor is indispensible for the establishment of the haematopoietic system. RUNX1 mediates the production of blood cells from endothelial cells which have haemogenic potential (haemogenic endothelium or HE) through a process termed endothelial to haematopoietic transition (EHT). Several studies have provided insights into the transcriptional programme governed by RUNX1 during EHT, suggesting that RUNX1 plays a role both in the activation of haematopoietic genes and inactivation of endothelial genes. However, due to the scarcity of cells and their transient nature, very little is known about whether RUNX1 influences the development of the HE itself. To this end, we adapted a technology, called DamID, to identify the very early genome-wide targets of RUNX1 in the HE. DamID is a methylation-based tagging technique where the Dam methylase (Dam) is fused to DNA binding proteins and stably marks their DNA binding sites. We generated RUNX1::Dam and control Dam expressing ES cell lines and purified cells at the onset of haematopoiesis and applied DamID coupled with high-throughput sequencing. To analyse the results we also developed a sequencing analysis pipeline specific for DamID data. We next correlated the RUNX1 binding sites with RNA-Seq expression data of the same cell populations. Our findings suggest, surprisingly, that at this very early stage of haematopoietic development RUNX1 positively regulates the endothelial gene expression programme. This up-regulation correlates with the formation of endothelial cell clusters, which precedes the generation of blood progenitors and corresponds to the development of HE. Overall, our results suggest a novel and unexpected role for RUNX1 in the establishment of HE that precedes its more established function in the EHT process." @default.
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- W2038238077 date "2013-08-01" @default.
- W2038238077 modified "2023-10-18" @default.
- W2038238077 title "Identification of the transcriptional programme controlled by RUNX1 in the haemogenic endothelium by utilising damid-seq" @default.
- W2038238077 doi "https://doi.org/10.1016/j.exphem.2013.05.094" @default.
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