title: Mtg16/Eto2 contributes to murine T-cell development.
abstract: Mtg16/Eto2 is a transcriptional corepressor that is disrupted by t(16;21) in acute myeloid leukemia. Using mice lacking Mtg16, we found that Mtg16 is a critical regulator of T-cell development. Deletion of Mtg16 led to reduced thymocyte development in vivo, and after competitive bone marrow transplantation, there was a nearly complete failure of Mtg16(-/-) cells to contribute to thymocyte development. This defect was recapitulated in vitro as Mtg16(-/-) Lineage(-)/Sca1(+)/c-Kit(+) (LSK) cells of the bone marrow or DN1 cells of the thymus failed to produce CD4(+)/CD8(+) cells in response to a Notch signal. Complementation of these defects by reexpressing Mtg16 showed that 3 highly conserved domains were somewhat dispensable for T-cell development but required the capacity of Mtg16 to suppress E2A-dependent transcriptional activation and to bind to the Notch intracellular domain. Thus, Mtg16 integrates the activities of signaling pathways and nuclear factors in the establishment of T-cell fate specification.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Aubrey
authors.initials: A
authors.lastname: Hunt
authors.forename: Melissa
authors.initials: M
authors.lastname: Fischer
authors.forename: Michael E
authors.initials: ME
authors.lastname: Engel
authors.forename: Scott W
authors.initials: SW
authors.lastname: Hiebert
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D005816:Genetic Complementation Test; D038041:Lymphopoiesis; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; C117411:Cbfa2t3 protein, mouse; C517750:TFPT protein, mouse; C489532:Tcf12 protein, mouse