PMID- 16415155
OWN - NLM
STAT- MEDLINE
DCOM- 20060317
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 4
DP  - 2006 Jan 24
TI  - The tumor suppressor menin regulates hematopoiesis and myeloid transformation by 
      influencing Hox gene expression.
PG  - 1018-23
AB  - Menin is the product of the tumor suppressor gene Men1 that is mutated in the 
      inherited tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Menin has 
      been shown to interact with SET-1 domain-containing histone 3 lysine 4 (H3K4) 
      methyltransferases including mixed lineage leukemia proteins to regulate homeobox 
      (Hox) gene expression in vitro. Using conditional Men1 knockout mice, we have 
      investigated the requirement for menin in hematopoiesis and myeloid 
      transformation. Men1 excision causes reduction of Hoxa9 expression, colony 
      formation by hematopoietic progenitors, and the peripheral white blood cell 
      count. Menin directly activates Hoxa9 expression, at least in part, by binding to 
      the Hoxa9 locus, facilitating methylation of H3K4, and recruiting the methylated 
      H3K4 binding protein chd1 to the locus. Consistent with signaling downstream of 
      menin, ectopic expression of both Hoxa9 and Meis1 rescues colony formation 
      defects in Men1-excised bone marrow. Moreover, Men1 excision also suppresses 
      proliferation of leukemogenic mixed lineage leukemia-AF9 
      fusion-protein-transformed myeloid cells and Hoxa9 expression. These studies 
      uncover an important role for menin in both normal hematopoiesis and myeloid 
      transformation and provide a mechanistic understanding of menin's function in 
      these processes that may be used for therapy.
FAU - Chen, Ya-Xiong
AU  - Chen YX
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson 
      Cancer Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
FAU - Yan, Jizhou
AU  - Yan J
FAU - Keeshan, Karen
AU  - Keeshan K
FAU - Tubbs, Anthony T
AU  - Tubbs AT
FAU - Wang, Haoren
AU  - Wang H
FAU - Silva, Albert
AU  - Silva A
FAU - Brown, Eric J
AU  - Brown EJ
FAU - Hess, Jay L
AU  - Hess JL
FAU - Pear, Warren S
AU  - Pear WS
FAU - Hua, Xianxin
AU  - Hua X
LA  - eng
GR  - R01 CA100912/CA/NCI NIH HHS/United States
GR  - CA100912/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060113
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chd1 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Histones)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (homeobox protein HOXA9)
RN  - 9007-49-2 (DNA)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Transformed
MH  - Cell Proliferation
MH  - Chromatin Immunoprecipitation
MH  - DNA/metabolism
MH  - DNA Methylation
MH  - DNA-Binding Proteins/metabolism
MH  - Exons
MH  - Flow Cytometry
MH  - *Gene Expression Regulation
MH  - Genotype
MH  - *Hematopoiesis
MH  - Histones/chemistry
MH  - Homeodomain Proteins/metabolism/*physiology
MH  - Homozygote
MH  - Leukemia/metabolism
MH  - Lysine/chemistry
MH  - Methylation
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Genetic
MH  - Models, Statistical
MH  - Myeloid Cells/metabolism
MH  - Proto-Oncogene Proteins/metabolism/*physiology
MH  - Retroviridae/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cells
MH  - Time Factors
MH  - Transgenes
PMC - PMC1326489
EDAT- 2006/01/18 09:00
MHDA- 2006/03/18 09:00
PMCR- 2006/01/24
CRDT- 2006/01/18 09:00
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2006/03/18 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
PHST- 2006/01/24 00:00 [pmc-release]
AID - 0510347103 [pii]
AID - 1018 [pii]
AID - 10.1073/pnas.0510347103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1018-23. doi: 
      10.1073/pnas.0510347103. Epub 2006 Jan 13.