SNF2beta-BRG1 is essential for the viability of F9 murine embryonal carcinoma cells.
The yeast and animal SNF-SWI and related multiprotein complexes are thought to play an important role in processes, such as transcription factor binding to regulatory elements, which require nucleosome remodeling in order to relieve the repressing effect of packaging DNA in chromatin. There are two mammalian homologs of the yeast SNF2-SWI2 subunit protein, SNF2alpha-brm and SNF2beta-BRG1, and overexpression of either one of them has been shown to enhance transcriptional activation by glucocorticoid, estrogen, and retinoic acid (RA) receptors in transiently transfected cells. We have investigated here the function of SNF2beta-BRG1 in the RA receptor-retinoid X receptor-mediated transduction of the retinoid signal in F9 embryonal carcinoma (EC) cells which differentiate into endodermal-like cells upon RA treatment. The two SNF2beta-BRG1 alleles have been targeted by homologous recombination and subsequently disrupted by using a conditional Cre recombinase. We show that F9 EC cells inactivated on both SNF2beta alleles are not viable and that heterozygous mutant cells are affected in proliferation but not in RA-induced differentiation. Thus, in F9 EC cells, SNF2beta-BRG1 appears to play an essential role in basal processes involved in cell proliferation, in addition to its putative role in the activation of transcription mediated by nuclear receptors.
Sumi-Ichinose
C
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Illkirch, CU de Strasbourg.
Ichinose
H
H
Metzger
D
D
Chambon
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D003001:Cloning, Molecular; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D054278:Embryonal Carcinoma Stem Cells; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology; D011995:Recombination, Genetic; D015183:Restriction Mapping; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; C084011:SMARCA2 protein, human; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; D014212:Tretinoin; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases