Small CTD phosphatases function in silencing neuronal gene expression.
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.
Yeo
Michele
M
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Lee
Soo-Kyung
SK
Lee
Bora
B
Ruiz
Esmeralda C
EC
Pfaff
Samuel L
SL
Gill
Gordon N
GN
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D000099229:RE1-Silencing Transcription Factor
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D014212:Tretinoin; D000099229:RE1-Silencing Transcription Factor; C102938:Neurog2 protein, mouse; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; C413483:CTDSP1 protein, human