title: Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence.
abstract: The t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Fischer
authors.forename: Isabel
authors.initials: I
authors.lastname: Moreno-Miralles
authors.forename: Aubrey
authors.initials: A
authors.lastname: Hunt
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Chyla
authors.forename: Scott W
authors.initials: SW
authors.lastname: Hiebert
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050703:E2F2 Transcription Factor; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C117411:Cbfa2t3 protein, mouse; C484940:E2f2 protein, mouse; C075668:Tcf3 protein, mouse