A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells
| Autor: | Thomas Mercher, Claudia Scholl, D. Gary Gilliland, Kristina Brumme, Jianing Liu, Nan Zhu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Chromatin Immunoprecipitation
Cancer Research Transcription Genetic Bone Marrow Cells Biology Real-Time Polymerase Chain Reaction Mice chemistry.chemical_compound Cell Line Tumor Genetics medicine Animals Humans Molecular Biology Histone Demethylases Gene knockdown Nuclear Proteins Cell Biology Hematology Flow Cytometry Embryonic stem cell Hematopoiesis Chromatin Haematopoiesis medicine.anatomical_structure RUNX1 chemistry Gene Knockdown Techniques Hematologic Neoplasms Cancer research Bone marrow Stem cell Chromatin immunoprecipitation |
| Zdroj: | Experimental Hematology. 40:487-498.e3 |
| ISSN: | 0301-472X |
| DOI: | 10.1016/j.exphem.2012.01.017 |
| Popis: | Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), an H3K27Me2/3 demethylase, has been implicated in development, self-renewal, and differentiation of various organs and embryonic stem cells through chromatin modifications and transcriptional regulation of important developmentally related genes, such as Hox genes. However, the function of UTX in hematopoiesis is not well understood. To study the role of UTX in the mammalian hematopoietic system, we used lentiviral short hairpin RNA constructs to knockdown UTX in the murine hematopoietic progenitor cell line EML, in primary murine bone marrow cells and in leukemic cell lines. We report that Utx is highly expressed in the hematopoietic compartment and that it plays an important role in cell proliferation and homeostasis of hematopoietic cells in vitro. Knockdown of UTX in EML and primary murine bone marrow cells impairs their colony-forming ability. Moreover, knockdown of UTX affects expression of key genes that regulate hematopoietic differentiation such as Mll1, Runx1, and Scl in primary murine bone marrow cells. And we further demonstrate that UTX directly associates with the promoters of the Mll1, Runx1, and Scl genes and modulate their transcription by controlling H3K27me3 marks on respective promoter regions. In addition, UTX depletion severely impaired proliferation of several human leukemia cell lines. Together, these data demonstrate a functional role for UTX in normal and malignant hematopoiesis. |
| Databáze: | OpenAIRE |
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