Small CTD phosphatases function in silencing neuronal gene expression

Michele Yeo, Soo Kyung Lee, Bora Lee, Esmeralda C. Ruiz, Samuel L. Pfaff, Gordon N. Gill

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

Neuronal gene transcription is repressed in non-neuronal cells by the repressor element 1 (RE-1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) complex. To understand how this silencing is achieved, we examined a family of class-C RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD) phosphatases [small CTD phosphatases (SCPs) 1 to 3], whose expression is restricted to non-neuronal tissues. We show that REST/NRSF recruits SCPs to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. Phosphatase-inactive forms of SCP interfere with REST/NRSF function and promote neuronal differentiation of P19 stem cells. Likewise, small interfering RNA directed to the single Drosophila SCP unmasks neuronal gene expression in S2 cells. Thus, SCP activity is an evolutionary conserved transcriptional regulator that acts globally to silence neuronal genes.

Original languageEnglish (US)
Pages (from-to)596-600
Number of pages5
JournalScience
Volume307
Issue number5709
DOIs
StatePublished - Jan 28 2005

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Yeo, M., Lee, S. K., Lee, B., Ruiz, E. C., Pfaff, S. L., & Gill, G. N. (2005). Small CTD phosphatases function in silencing neuronal gene expression. Science, 307(5709), 596-600. https://doi.org/10.1126/science.1100801