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Science 307 (5709): 596-600

Copyright © 2005 by the American Association for the Advancement of Science

Small CTD Phosphatases Function in Silencing Neuronal Gene Expression

Michele Yeo,1*{dagger} Soo-Kyung Lee,2*{ddagger} Bora Lee,2{ddagger} Esmeralda C. Ruiz,2 Samuel L. Pfaff,2 Gordon N. Gill1§

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 evolutionarily conserved transcriptional regulator that acts globally to silence neuronal genes.

1 Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
2 The Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.

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* These two authors contributed equally to this work.

{dagger} Present address: Neurology Division, Duke University Medical Center, Durham, NC 27710, USA.

{ddagger} Present address: Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Room 132C, Houston, TX 77030, USA.

§ To whom correspondence should be addressed. E-mail: ggill{at}ucsd.edu

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