A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes.
Mammalian SWI/SNF complexes utilize either brahma (Brm) or brahma-related gene 1 (Brg1) catalytic subunits to remodel nucleosomes in an ATP-dependent manner. Brm was previously shown to be dispensable, suggesting that Brm and Brg1 are functionally redundant. To test this hypothesis, we have generated a Brg1 null mutation by gene targeting, and, surprisingly, homozygotes die during the periimplantation stage. Furthermore, blastocyst outgrowth studies indicate that neither the inner cell mass nor trophectoderm survives. However, experiments with other cell types demonstrate that Brg1 is not a general cell survival factor. In addition, Brg1 heterozygotes are predisposed to exencephaly and tumors. These results provide evidence that biochemically similar chromatin-remodeling complexes have dramatically different functions during mammalian development.
Bultman
S
S
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
Gebuhr
T
T
Yee
D
D
La Mantia
C
C
Nicholson
J
J
Gilliam
A
A
Randazzo
F
F
Metzger
D
D
Chambon
P
P
Crabtree
G
G
Magnuson
T
T
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D018797:Cell Cycle Proteins; D002470:Cell Survival; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D020964:Embryo Loss; D005347:Fibroblasts; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020043:Genes, Essential / Q000235:genetics; D006579:Heterozygote; D006651:Histocytochemistry; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499503:Smarca2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; C513194:Smarca4 protein, mouse; D004265:DNA Helicases