Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian polycomb complex.
The Bmi1 gene has been identified as a mouse Polycomb group (Pc-G) gene implicated in the regulation of Hox gene expression. Here we describe the characterization of a Bmi binding protein Mph1, which shares similarity to Drosophila polyhomeotic. Coimmunoprecipitation experiments indicate that Bmi1 and Mph1, as well as the Mel18 and M33 proteins described previously, are constituents of a multimeric protein complex in mouse embryos and human cells. A central domain of Bmi1 interacts with the carboxyl terminus of Mph1, whereas a conserved alpha-helical domain in the Mph1 protein is required for its homodimerization. Transgenic mice overexpressing various mutant Bmi1 proteins demonstrate that the central domain of Bmil is required for the induction of anterior transformations of the axial skeleton. Bmi1, M33, and Mph1 show an overlapping speckled distribution in interphase nuclei. These data provide molecular evidence for the existence of a mammalian Polycomb complex.
Alkema
M J
MJ
The Netherlands Cancer Institute Division of Molecular Genetics, Amsterdam.
Bronk
M
M
Verhoeven
E
E
Otte
A
A
van 't Veer
L J
LJ
Berns
A
A
van Lohuizen
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila; D029721:Drosophila Proteins; D019077:Helix-Turn-Helix Motifs; D019476:Insect Proteins / Q000378:metabolism; D007399:Interphase; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009698:Nucleoproteins / Q000737:chemistry / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D016415:Sequence Alignment
C489421:Bmi1 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D009698:Nucleoproteins; C489348:PCGF2 protein, human; C491239:PHC1 protein, human; C066770:Pc protein, Drosophila; C066476:Pcgf6 protein, mouse; C103827:Phc1 protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1