1: Genes Dev. 2008 Mar 1;22(5):601-14.
Related Articles, Links
Epigenetic regulation of gene expression by Drosophila Myb and
E2F2-RBF via the Myb-MuvB/dREAM complex.
Wen H, Andrejka L, Ashton J, Karess R, Lipsick JS.
Department of Pathology and Department of Genetics, Stanford University, Stanford, CA
94305, USA.
The Drosophila Myb oncoprotein, the E2F2 transcriptional repressor, and the RBF and
Mip130/LIN-9 tumor suppressor proteins reside in a conserved Myb-MuvB
(MMB)/dREAM complex. We now show that Myb is required in vivo for the expression
of Polo kinase and components of the spindle assembly checkpoint (SAC). Surprisingly,
the highly conserved DNA-binding domain was not essential for assembly of Myb into
MMB/dREAM, for transcriptional regulation in vivo, or for rescue of Myb-null mutants
to adult viability. E2F2, RBF, and Mip130/LIN-9 acted in opposition to Myb by
repressing the expression of Polo and SAC genes in vivo. Remarkably, the absence of
both Myb and Mip130, or of both Myb and E2F2, caused variegated expression in which
high or low levels of Polo were stably inherited through successive cell divisions in
imaginal wing discs. Restoration of Myb resulted in a uniformly high level of Polo
expression similar to that seen in wild-type tissue, whereas restoration of Mip130 or E2F2
extinguished Polo expression. Our results demonstrate epigenetic regulation of gene
expression by Myb, Mip130/LIN-9, and E2F2-RBF in vivo, and also provide an
explanation for the ability of Mip130-null mutants to rescue the lethality of Myb-null
mutants in vivo.
Publication Types:
 Research Support, N.I.H., Extramural
 Research Support, Non-U.S. Gov't
PMID: 18316477 [PubMed - indexed for MEDLINE]
PMCID: PMC2259030 [Available on 09/01/08]
2: Nat Cell Biol. 2007 May;9(5):581-7. Epub 2007 Apr 22.
Related Articles, Links
Loss of Drosophila Myb
chromosome condensation.
interrupts
the
progression
of
Manak JR, Wen H, Van T, Andrejka L, Lipsick JS.
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive,
Stanford, CA 94305-5342, USA.
Completion of chromosome condensation is required before segregation during the
mitotic cell cycle to ensure the transmission of genetic material with high fidelity in a
timely fashion. In many eukaryotes this condensation is regulated by phosphorylation of
histone H3 on Ser 10 (H3S10). This phosphorylation normally begins in the
late-replicating pericentric heterochromatin and then spreads to the earlier replicating
euchromatin. Here, we show that these phases of condensation are genetically separable
in that the absence of Drosophila Myb causes cells to arrest with H3S10 phosphorylation
of heterochromatin but not euchromatin. In addition, we used mosaic analysis to
demonstrate that although the Myb protein can be removed in a single cell cycle, the
failure of chromosome condensation occurs only after many cell divisions in the absence
of Myb protein. The Myb protein is normally located in euchromatic but not
heterochromatic regions of the nucleus, suggesting that Myb may be essential for a
modification of euchromatin that is required for the efficient spread of chromosome
condensation.
Publication Types:
 Research Support, N.I.H., Extramural
PMID: 17450131 [PubMed - indexed for MEDLINE]
3: Mol Cancer. 2006 Nov 2;5:54.
Related Articles, Links
Myb proteins inhibit fibroblast transformation by v-Rel.
Fu SL, Ganter B, Lipsick JS.
Departments of Pathology and Genetics, Stanford University School of Medicine, 300
Pasteur Drive, Stanford, CA 94305-5324, USA. slfu@ym.edu.tw
Genes that cause cancer have been divided into two general classes--oncogenes that act in
a dominant fashion to transform normal cells into a malignant state, and tumor suppressor
genes that act in a dominant fashion to prevent such transformation. In this report, we
demonstrate that both the v-myb retroviral oncogene, which causes leukemic
transformation of hematopoietic cells, and the c-myb proto-oncogene can also function as
inhibitors of fibroblast transformation by the v-rel oncogene. These results imply that the
myb genes can function either as oncogenes or as tumor suppressors in different cellular
contexts.
Publication Types:
 Research Support, N.I.H., Extramural
PMID: 17081304 [PubMed - indexed for MEDLINE]
PMCID: PMC1635057
4: Oncogene. 2007 Feb 22;26(8):1238-44. Epub 2006 Aug 14.
Related Articles, Links
v-Myb represses the transcription of Ets-2.
Wang DM, Sevcikova S, Wen H, Roberts S, Lipsick JS.
Department of Pathology, Stanford University School of Medicine, Stanford, CA
94305-5324, USA.
The v-Myb oncogene causes monoblastic leukemia and transforms only myelomonocytic
cells in culture. The v-Myb protein is nuclear and binds to specific DNA sequences. To
identify genes regulated by v-Myb, we utilized primary cells transformed by a retrovirus
encoding a v-Myb-estrogen receptor (ER) fusion protein. The Ets-2 gene was not
expressed in v-Myb-ER transformed cells in the presence of estradiol, but was expressed
within 4 h after estradiol withdrawal. The expression of Ets-2 also increased dramatically
following phorbol ester-induced differentiation of the v-Myb-transformed BM2 cell line.
Conversely, CRYP-alpha, encoding a transmembrane tyrosine phosphatase, was
expressed in the presence but not the absence of estradiol in v-Myb-ER transformed cells.
CRYP-alpha was downregulated during the phorbol ester-induced differentiation of BM2
cells. Although LIM-3 expression was estradiol-inducible in v-Myb-ER transformed
monoblasts, LIM-3 was expressed neither in primary yolk sac cells transformed by
unfused v-Myb nor in BM2 cells. We conclude that although v-Myb has been intensively
studied as a transcriptional activator, v-Myb can repress biologically relevant genes such
as Ets-2, which promotes macrophage differentiation. In addition, we have shown that
some genes that are regulated by a v-Myb-ER fusion protein may not be relevant to the
biological function of the unfused v-Myb protein.
Publication Types:
 Research Support, N.I.H., Extramural
PMID: 16909100 [PubMed - indexed for MEDLINE]
Research interest: Drosophila Myb function
Current interest: epigenetic regulation
Epigenetic regulation of gene expression by Drosophila Myb and
E2F2-RBF via the Myb-MuvB/dREAM complex.
MybPolo kinase and components of the spindle assembly checkpoint (SAC).
Myb MMB/dREAM,
Loss of Drosophila Myb interrupts the progression of chromosome
condensation.
Completion of chromosome condensation is required before segregation during the mitotic cell
cycle to ensure the transmission of genetic material with high fidelity in a timely fashion.
Here, we show that these phases of condensation are genetically separable in that the absence of
Drosophila Myb causes cells to arrest with H3S10 phosphorylation of heterochromatin but not
euchromatin.
myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts.