title: The leucine zipper region of Myb oncoprotein regulates the commitment of hematopoietic progenitors.
abstract: The development of blood cells proceeds from pluripotent stem cells through multipotent progenitors into mature elements belonging to at least 8 different lineages. The lineage choice process during which stem cells and progenitors commit to a particular lineage is regulated by a coordinated action of extracellular signals and transcription factors. Molecular mechanisms controlling commitment are largely unknown. Here, the transcription factor v-Myb and its leucine zipper region (LZR) are identified as regulators of the commitment of a common myeloid progenitor and progenitors restricted to the myeloid lineage. It is demonstrated that wild-type v-Myb with the intact LZR directs development of progenitors into the macrophage lineage. Mutations in this region compromise commitment toward myeloid cells and cause v-Myb to also support the development of erythroid cells, thrombocytes, and granulocytes, similar to the c-Myb protein. In agreement with that, the wild-type v-Myb induces high expression of myeloid factors C/EBP beta, PU.1, and Egr-1 in its target cells, whereas SCL, GATA-1, and c-Myb are more abundant in cells expressing the v-Myb LZR mutant. It is proposed that Myb LZR can function as a molecular switch, affecting expression of lineage-specifying transcription factors and directing the development of hematopoietic progenitors into either myeloid or erythroid lineages.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
authors.forename: V
authors.initials: V
authors.lastname: Karafiát
authors.forename: M
authors.initials: M
authors.lastname: Dvoráková
authors.forename: P
authors.initials: P
authors.lastname: Pajer
authors.forename: J
authors.initials: J
authors.lastname: Králová
authors.forename: Z
authors.initials: Z
authors.lastname: Horejsí
authors.forename: V
authors.initials: V
authors.lastname: Cermák
authors.forename: P
authors.initials: P
authors.lastname: Bartůnek
authors.forename: M
authors.initials: M
authors.lastname: Zenke
authors.forename: M
authors.initials: M
authors.lastname: Dvorák
mesh_terms: D000818:Animals; D001792:Blood Platelets; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002642:Chick Embryo; D004912:Erythrocytes; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006098:Granulocytes; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D016350:Leucine Zippers; D008264:Macrophages; D009154:Mutation; D020626:Oncogene Proteins v-myb / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D020626:Oncogene Proteins v-myb