title: An ENU-induced point mutation in the mouse Btaf1 gene causes post-gastrulation embryonic lethality and protein instability.
abstract: The mouse Btaf1 gene, an ortholog of yeast MOT1, encodes a highly conserved general transcription factor. The function of this SNF2-like ATPase has been studied mainly in yeast and human cells, which has revealed that it binds directly to TBP, forming the B-TFIID complex. This complex binds to core promoters of RNA polymerase II-transcribed genes and, of crucial importance, BTAF1-TBP interactions have been shown to affect the kinetics of TBP-promoter interactions. Here we report the isolation of a mouse line carrying a Btaf1 allele containing an ENU-induced point mutation that causes a substitution mutation in the BTAF1 ATPase domain. Embryos homozygous for this loss-of-function mutation appear to be morphologically normal until early somite stages, but die between embryonic days 9 and 10.5 displaying growth arrest and edema. Analyses in vitro suggest that the altered protein is less stable and, independent from this, functionally impaired in releasing of TBP from chromatin, but not in binding to TBP.
authors.affiliation: Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan, Netherlands.
authors.forename: Carolien
authors.initials: C
authors.lastname: Wansleeben
authors.forename: Léon
authors.initials: L
authors.lastname: van Gurp
authors.forename: Petra
authors.initials: P
authors.lastname: de Graaf
authors.forename: Florence
authors.initials: F
authors.lastname: Mousson
authors.forename: H Th
authors.initials: HT
authors.lastname: Marc Timmers
authors.forename: Frits
authors.initials: F
authors.lastname: Meijlink
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D005038:Ethylnitrosourea; D005260:Female; D054262:Gastrulation; D020869:Gene Expression Profiling; D005804:Genes, Lethal; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D050505:Mutant Proteins / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C561880:BTAF1 protein, mouse; D002843:Chromatin; D050505:Mutant Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D005038:Ethylnitrosourea