Small CTD phosphatases function in silencing neuronal gene expression

Science. 2005 Jan 28;307(5709):596-600. doi: 10.1126/science.1100801.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Silencing*
  • Humans
  • In Situ Hybridization
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / physiology*
  • Nuclear Proteins
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • RNA Interference
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism*
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • Nuclear Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • Tretinoin
  • CTDSP1 protein, human
  • Phosphoprotein Phosphatases