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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3668-3676
HEMATOPOIESIS
The leucine zipper region of Myb oncoprotein regulates the
commitment of hematopoietic progenitors
Vít Karafiát,
Marta Dvo áková,
Petr Pajer,
Jarmila Králová,
Zuzana Ho ej í,
Vladimír ermák,
Petr Bart n k,
Martin Zenke, and
Michal Dvo ák
From the Institute of Molecular Genetics, Academy of
Sciences of the Czech Republic, Prague, and the Max-Delbrück
Center for Molecular Medicine, Berlin, Germany.
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 , 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.

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