Decoding transcriptional repressor complexes in the adult central nervous system

Neuropharmacology. 2014 May;80:45-52. doi: 10.1016/j.neuropharm.2013.12.024. Epub 2014 Jan 10.

Abstract

Cells maintain precise gene expression by balancing transcriptional activation and repression. While much work has focused on elucidating transcriptional activation in the central nervous system (CNS), little is known about transcriptional repression. One means to repress gene expression is to initiate binding of transcription factors to DNA, which then recruit co-repressors as well as other accessory proteins, forming a multi-protein repressor complex. These multi-protein repressor complexes include histone modifying enzymes that trigger processes such as histone acetylation, methylation, and ubiquitylation, altering chromatin structures to impact gene expression. Within these complexes transcriptional repressor proteins per se do not exhibit enzymatic reactions to remodel chromatin structure, whereas histone modifying enzymes lack intrinsic DNA binding activity but have an ability to process post-translational modifications on histones. Thus, the mutual association between transcriptional repressors and histone modifying enzymes is essential to sculpt chromatin to favor transcriptional repression and down regulate gene expression. Additionally, co-repressors are integral components in the context of gene repression as they bridge the association of transcriptional repressors and histone modifying enzymes. In this review, we will discuss the roles of some of the major components of these repressor complex in the CNS as well as their cellular functions that may underlie fundamental behavior in animals.

Keywords: Behavior; CNS; HDACs; MeCP2; REST; Synapse; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Animals
  • Central Nervous System / enzymology
  • Central Nervous System / metabolism*
  • Chromatin Assembly and Disassembly
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism*
  • Epigenetic Repression*
  • Gene Expression Regulation
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / enzymology
  • Neurons / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*

Substances

  • Co-Repressor Proteins
  • Isoenzymes
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Nerve Tissue Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Histone Deacetylases