MPc2, a new murine homolog of the Drosophila polycomb protein is a member of the mouse polycomb transcriptional repressor complex.
The evolutionarily conserved polycomb and trithorax-group genes are required to maintain stable expression patterns of homeotic genes and other target genes throughout development. Here, we report the cloning and characterization of a novel mouse polycomb homolog, MPc2, in addition to the previously described M33 polycomb gene. Co-immunoprecipitations and subnuclear co-localization studies show that MPc2 interacts with the mouse polycomb-group oncoprotein Bmi1 and is a new member of the mouse polycomb multiprotein complex. Gal4DB-MPc2 or -M33 fusion proteins mediate a five- to tenfold repression of stably integrated reporter constructs carrying GAL4 binding sites, demonstrating that these proteins are transcriptional repressors. The MPc2 gene is localized on chromosome 11, in close proximity to the classical mouse mutations tail short (Ts) and rabo torcido (Rbt). Ts and Rbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of phenotypes observed in mice with mutated polycomb or trithorax-group genes, suggesting that MPc2 is a candidate gene for Ts and Rbt.
Alkema
M J
MJ
The Netherlands Cancer Institute and Department of Biochemistry, University of Amsterdam, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Jacobs
J
J
Voncken
J W
JW
Jenkins
N A
NA
Copeland
N G
NG
Satijn
D P
DP
Otte
A P
AP
Berns
A
A
van Lohuizen
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D016384:Consensus Sequence; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005796:Genes; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014158:Transcription, Genetic
C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; C570426:Cbx2 protein, mouse; D018076:DNA, Complementary; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1