Precise control of hematopoietic stem cell (HSC) proliferation and differentiation is needed to maintain a lifetime supply of blood cells. Using genome-wide ENU mutagenesis and phenotypic screening, we have identified a mouse line that harbors a point mutation in the transactivation (TA) domain of the transcription factor c-Myb (M303V), which reduces c-Myb-dependent TA by disrupting its interac...

The c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanki...

The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. R2R3-MYB family members regulate plant-specific processes, such as the elaboration of specialized cell types, including xylem, guard cells, trichomes, and root hairs, and the biosynthesis of specialized branches of metabolism, including phenylpropanoid biosynthesis. As such, R2R3-MYB family members ar...

In murine leukemia virus-induced myeloid leukemias, insertional mutagenesis of the c-myb locus has been shown to occur frequently. Proto-oncogene activation is achieved in most leukemias by integration of murine leukemia virus upstream of exons 3 or 4 or by integration into exon 9 with consequent truncation of the protein. The present study investigates the effect of ectopic expression of full-...

In Arabidopsis, a MYB-bHLH-WD40 (MBW) transcriptional activator complex activates the homeodomain protein gene GLABRA2 (GL2), leading to the promotion of trichome formation and inhibition of root hair formation. The same MBW complex also activates single-repeat R3 MYB genes. R3 MYBs in turn, play a negative feedback role by competing with R2R3 MYB proteins for binding bHLH proteins, thus blocki...

RATIONALE c-myb null (knockout) embryonic stem cells (ESC) can differentiate into cardiomyocytes but not contractile smooth muscle cells (SMC) in embryoid bodies (EB). OBJECTIVE To define the role of c-Myb in SMC differentiation from ESC. METHODS AND RESULTS In wild-type (WT) EB, high c-Myb levels on days 0-2 of differentiation undergo ubiquitin-mediated proteosomal degradation on days 2.5-...

The cell-cycle-regulated Myb-family transcription factor B-Myb is crucial during S phase in many diploid cell types. We have examined the expression and function of B-Myb in megakaryocytic differentiation, during which cells progress from a diploid to a polyploid state. In contrast to terminal differentiation of most haematopoietic cells, during which B-myb is rapidly downregulated, differentia...

Although hematopoietic precursor activity can be generated in vitro from human embryonic stem cells, there is no solid evidence for the appearance of multipotent, self-renewing and transplantable hematopoietic stem cells. This could be due to short half-life of hematopoietic stem cells in culture or, alternatively, human embryonic stem cell-initiated hematopoiesis may be hematopoietic stem cell...

The c-Myb transcription factor is a critical regulator of proliferation and stem cell differentiation, and mutated alleles of c-Myb are oncogenic, but little is known about changes in c-Myb activity during the cell cycle. To map the association of c-Myb with specific target genes during the cell cycle, we developed a novel Fix-Sort-ChIP approach, in which asynchronously growing cells were fixed...

Reduced expression of the proto-oncogene c-myb appears necessary for erythroid differentiation induced by chemical agents and by the natural regulator, erythropoietin (Epo). Treatment of Epo-responsive Rauscher erythroleukemia cells with an anti-sense oligodeoxynucleotide to c-myb in the absence of other inducers downregulated myb protein markedly and caused hemoglobinization of the cells withi...