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B6: The role of UTX in hematopoiesis

Project leader:  Dr. S. Brenner

Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. Based on an shRNA library screening assay, we have identified the histone 3 lysine 27 demethylase UTX as a novel regulator for hematopoietic cell migration. Using hematopoietic stem and progenitor cells from our conditional UTX-knockout mouse, we were able to confirm the regulatory function of UTX on cell migration. Moreover, adult conditional UTX-knockout female mice displayed defective hematopoiesis in the bone marrow and splenic erythropoiesis whereas UTX-knockout males showed no phenotype. During development, all UTX-knockout female and a portion of UTX-knockout male embryos developed a cardiac defect, cranioschisis and died in utero.

Thus, UTY, the male homologue of UTX can partially compensate for UTX, despite its absent histone-demethylase activity. Using our UTX-knockout mouse model, we aim to study the role of UTX on the formation of the hematopoietic cell niche during embryonic and adult hematopoiesis. To study potential histone-demethylase independent functions of UTX, we will analyse UTX localisation and interaction partners, and will investigate the influence of histone-demethylase mutants of UTX on stem cell differentiation. Our studies will provide insights into the role of UTX for the hematopoietic system as well as its proposed histone-demethylase independent functions.

« January 2020 »

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