RE-1 silencing transcription factor-4 (REST4) is neither a transcriptional repressor nor a de-repressor

Neurochem Int. 2002 Mar;40(3):195-202. doi: 10.1016/s0197-0186(01)00091-2.


The zinc finger protein RE-1 silencing transcription factor (REST) is a transcriptional repressor that represses neuronal genes in non-neuronal tissues. A neuronal splice form of REST, termed REST4, has been described in the rat. It encompasses the N-terminus of REST, including the N-terminal repressor domain and five of the eight zinc fingers of the DNA-binding domain. The biological function of REST4 is controversial. Transcriptional repression as well as transcriptional de-repression activity has been attributed to the REST4 protein of rat. Here, we have expressed a 'humanized' version of REST4 (hREST4) to facilitate a comparison of the biological functions of hREST4 and REST. The biological activity the human REST protein has been extensively studied in the past. Additionally, hREST4 has a high degree of homology with the REST4 protein of rat. An immunofluorescence analysis showed that hREST4 is expressed in the nucleus, indicating that the protein may have a potential impact on gene regulation. We analyzed the biological function of hREST4 in NS20Y neuroblastoma cells using human synapsin I promoter/reporter gene constructs. The human synapsin I gene is negatively regulated by REST. The results show that hREST4, in contrast to the full-length human REST protein, does not impair human synapsin I promoter activity. Moreover, co-transfection experiments with expression vectors encoding REST and hREST4 did not reveal any evidence that REST4 blocks the transcriptional repression activity of REST.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Gene Expression
  • Humans
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Synapsins / genetics
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic / physiology*
  • Tumor Cells, Cultured
  • Zinc Fingers / physiology


  • RE1-silencing transcription factor
  • Repressor Proteins
  • Synapsins
  • Transcription Factors