PMID- 19393316
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20211028
IS  - 1872-6356 (Electronic)
IS  - 0925-4773 (Print)
IS  - 0925-4773 (Linking)
VI  - 126
IP  - 7
DP  - 2009 Jul
TI  - In vitro hematopoietic differentiation of mouse embryonic stem cells requires the 
      tumor suppressor menin and is mediated by Hoxa9.
PG  - 517-22
LID - 10.1016/j.mod.2009.04.001 [doi]
AB  - Inactivating mutations in the tumor suppressor gene MEN1 cause the inherited 
      cancer syndrome multiple endocrine neoplasia type 1 (MEN1). The ubiquitously 
      expressed MEN1 encoded protein, menin, interacts with MLL (mixed-lineage leukemia 
      protein), and together they are essential components of a multiprotein complex 
      with histone methyl transferase activity. MLL is also essential for 
      hematopoiesis, and plays a critical role in leukemogenesis via epigenetic 
      regulation of Hoxa9 expression that also requires menin. Therefore we chose to 
      explore the role of menin in hematopoiesis. We generated Men1(-/-) embryonic stem 
      (ES) cell lines, and induced them to differentiate in vitro. While these cells 
      were able to form embryoid bodies (EBs) expressing the early markers Flk-1 and 
      c-Kit, their ability to further differentiate into hematopoietic colonies was 
      compromised. The Men1(-/-) ES cells show reduced expression of Hoxa9 that can be 
      recovered by reexpression of Menin. We demonstrate that the block in 
      differentiation of Men1(-/-) ES cell lines can be rescued not only by the 
      expression of menin but also that of Hoxa9. These results suggest that, similar 
      to MLL, menin is required for hematopoiesis, and this requirement may be mediated 
      through regulation of Hoxa9 expression.
FAU - Novotny, Elizabeth
AU  - Novotny E
AD  - Genome Technology Branch, National Human Genome Research Institute, National 
      Institutes of Health, Bethesda, MD 20892, USA.
FAU - Compton, Sheila
AU  - Compton S
FAU - Liu, P Paul
AU  - Liu PP
FAU - Collins, Francis S
AU  - Collins FS
FAU - Chandrasekharappa, Settara C
AU  - Chandrasekharappa SC
LA  - eng
GR  - Z01 HG000029-13/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20090422
PL  - Ireland
TA  - Mech Dev
JT  - Mechanisms of development
JID - 9101218
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (homeobox protein HOXA9)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Embryonic Stem Cells/*cytology/*metabolism
MH  - Gene Expression Regulation, Developmental
MH  - *Hematopoiesis
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Mice
MH  - Proto-Oncogene Proteins/deficiency/*metabolism
MH  - Tumor Suppressor Proteins/*metabolism
PMC - PMC2717021
MID - NIHMS111099
EDAT- 2009/04/28 09:00
MHDA- 2009/10/09 06:00
PMCR- 2010/07/01
CRDT- 2009/04/28 09:00
PHST- 2008/11/21 00:00 [received]
PHST- 2009/03/22 00:00 [revised]
PHST- 2009/04/11 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S0925-4773(09)00044-6 [pii]
AID - 10.1016/j.mod.2009.04.001 [doi]
PST - ppublish
SO  - Mech Dev. 2009 Jul;126(7):517-22. doi: 10.1016/j.mod.2009.04.001. Epub 2009 Apr 
      22.