title: RE-1 silencing transcription factor-4 (REST4) is neither a transcriptional repressor nor a de-repressor.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421, Homburg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Magin
authors.forename: Michael
authors.initials: M
authors.lastname: Lietz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cibelli
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016704:Synapsins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000502:physiology; D000099229:RE1-Silencing Transcription Factor
chemical_list: D012097:Repressor Proteins; D016704:Synapsins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor