title: PBX1 is dispensable for neural commitment of RA-treated murine ES cells.
abstract: Experimentation with PBX1 knockout mice has shown that PBX1 is necessary for early embryogenesis. Despite broad insight into PBX1 function, little is known about the underlying target gene regulation. Utilizing the Cre-loxP system, we targeted a functionally important part of the homeodomain of PBX1 through homozygous deletion of exon-6 and flanking intronic regions leading to exon 7 skipping in embryonic stem (ES) cells. We induced in vitro differentiation of wild-type and PBX1 mutant ES cells by aggregation and retinoic acid (RA) treatment and compared their profiles of gene expression at the ninth day post-reattachment to adhesive media. Our results indicate that PBX1 interactions with HOX proteins and DNA are dispensable for RA-induced ability of ES to express neural genes and point to a possible involvement of PBX1 in the regulation of imprinted genes.
authors.affiliation: Department of Medicine I, University of Freiburg Medical Center, Hugstetter Str. 55, 79106, Freiburg, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Jürgens
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kolanczyk
authors.forename: Dietrich C C
authors.initials: DC
authors.lastname: Moebest
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zemojtel
authors.forename: Urs
authors.initials: U
authors.lastname: Lichtenauer
authors.forename: Marlena
authors.initials: M
authors.lastname: Duchniewicz
authors.forename: Melanie P
authors.initials: MP
authors.lastname: Gantert
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Uwe
authors.initials: U
authors.lastname: Hattenhorst
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.forename: Annette
authors.initials: A
authors.lastname: Dorn
authors.forename: Mark P
authors.initials: MP
authors.lastname: Kamps
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Daniel
authors.initials: D
authors.lastname: Räpple
authors.forename: Jürgen S
authors.initials: JS
authors.lastname: Scheele
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004475:Ectoderm / Q000187:drug effects / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018390:Gene Targeting; D018392:Genomic Imprinting / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D007438:Introns / Q000235:genetics; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011995:Recombination, Genetic / Q000187:drug effects; D017384:Sequence Deletion / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D018398:Homeodomain Proteins; D050505:Mutant Proteins; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors; D014212:Tretinoin; C045073:Cre recombinase; D019426:Integrases