Loss- and gain-of-function mutations show a polycomb group function for Ring1A in mice.
The products of the Polycomb group (PcG) of genes act as transcriptional repressors involved in the maintenance of homeotic gene expression patterns throughout development, from flies to mice. Biochemical and molecular evidence suggests that the mouse Ring1A gene is a member of the PcG of genes. However, genetic evidence is needed to establish PcG function for Ring1A, since contrary to all other murine PcG genes, there is no known Drosophila PcG gene encoding a homolog of the Ring1A protein. To study Ring1A function we have generated a mouse line lacking Ring1A and mouse lines overexpressing Ring1A. Both Ring1A(-/-)and Ring1A(+/-) mice show anterior transformations and other abnormalities of the axial skeleton, which indicates an unusual sensitivity of axial skeleton patterning to Ring1A gene dosage. Ectopic expression of Ring1A also results in dose-dependent anterior transformations of vertebral identity, many of which, interestingly, are shared by Ring1A(-/-) mice. In contrast, the alterations of Hox gene expression observed in both type of mutant mice are subtle and involve a reduced number of Hox genes. Taken together, these results provide genetic evidence for a PcG function of the mouse Ring1A gene.
del Mar Lorente
M
M
Developmental and Cell Biology, Centro de Investigaciones Biológicas, Velázquez 144, Spain.
Marcos-Gutiérrez
C
C
Pérez
C
C
Schoorlemmer
J
J
Ramírez
A
A
Magin
T
T
Vidal
M
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016296:Mutagenesis; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000502:physiology*; D012272:Ribs / Q000002:abnormalities*; D013131:Spine / Q000002:abnormalities*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C490669:HOXB8 protein, human; C118987:HOXC5 protein, human; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; C484111:Hoxa4 protein, mouse; C513262:Hoxb4 protein, mouse; C095822:Hoxb8 protein, mouse; C490904:Hoxc4 protein, mouse; C489816:Hoxc8 protein, mouse; C490939:Hoxd11 protein, mouse; C489520:Hoxd4 protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489831:hoxa2b protein, zebrafish; C099223:hoxd10a protein, zebrafish; D063150:Polycomb Repressive Complex 1; C489840:Ring1 protein, mouse