title: Transcriptional elongation factor elongin A regulates retinoic acid-induced gene expression during neuronal differentiation.
abstract: Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A(-/-)) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A(-/-) embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A(-/-) ESCs.
authors.affiliation: Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasukawa
authors.forename: Shachi
authors.initials: S
authors.lastname: Bhatt
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Junya
authors.initials: J
authors.lastname: Kawauchi
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Takahashi
authors.forename: Aya
authors.initials: A
authors.lastname: Tsutsui
authors.forename: Takuya
authors.initials: T
authors.lastname: Muraoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsuda
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Kitajima
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.forename: Paul A
authors.initials: PA
authors.lastname: Trainor
authors.forename: Teijiro
authors.initials: T
authors.lastname: Aso
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D000075065:Elongin; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D016415:Sequence Alignment; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C000616403:Eloa protein, mouse; D000075065:Elongin; D014157:Transcription Factors; D014212:Tretinoin; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II; C522173:Rpb1 protein, mouse