Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

Autor: Takashi Yasukawa, Shachi Bhatt, Tamotsu Takeuchi, Junya Kawauchi, Hidehisa Takahashi, Aya Tsutsui, Takuya Muraoka, Makoto Inoue, Masayuki Tsuda, Shigetaka Kitajima, Ronald C. Conaway, Joan W. Conaway, Paul A. Trainor, Teijiro Aso
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Cell Reports, Vol 2, Iss 5, Pp 1129-1136 (2012)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2012.09.031
Popis: 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.
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