title: Biological activity of mammalian transcriptional repressors.
abstract: Research on the regulation of transcription in mammals has focused in recent years mainly on the mechanism of transcriptional activation. However, transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and might play an important role in many biological processes. To understand the molecular mechanism of transcriptional repression, the activity of eight mammalian repressors or repressor domains was investigated using a set of model promoters in combination with two different transcriptional detection methods. The repressors studied were: REST, the thyroid hormone receptors alpha and beta, the zinc finger protein NK10 containing a 'krüppel-associated box' (KRAB), repressor domains derived from the proteins Egr-1, Oct2A and Dr1 and the repressor/activator protein YY1. Here we show that the repressor domains of REST, Egr-1, the thyroid hormone receptors alpha< and beta and NK10 were transferable to a heterologous DNA-binding domain and repressed transcription from proximal and distal positions. Moreover, these repressor domains also blocked the activity of a strong viral enhancer in a 'remote position'. Thus, these domains are 'general' transcriptional repressor domains. The 'krüppel-associated box' was the most powerful repressor domain tested. In contrast, the repressor domains derived from Oct2A and Dr1 were inactive when fused to a heterologous DNA-binding domain. The repressor domain of YY1 exhibited transcriptional repression activity only in one of the transcriptional assay systems. The recruitment of histone deacetylases to the proximity of the basal transcriptional apparatus was recently discussed as a mechanism for some mammalian transcriptional repressor proteins. Here we show here that histone deacetylase 2, targeted to the reporter gene via DNA-protein interaction, functions as a transcriptional repressor protein regardless of the location of its binding site within the transcription unit.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical School, Homburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Thiel
authors.forename: M
authors.initials: M
authors.lastname: Lietz
authors.forename: K
authors.initials: K
authors.lastname: Bach
authors.forename: L
authors.initials: L
authors.lastname: Guethlein
authors.forename: G
authors.initials: G
authors.lastname: Cibelli
mesh_terms: D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D050981:Erythroid-Specific DNA-Binding Factors; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D008322:Mammals; D050813:Octamer Transcription Factor-2; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D050986:YY1 Transcription Factor; D000099229:RE1-Silencing Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D050981:Erythroid-Specific DNA-Binding Factors; D005656:Fungal Proteins; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D017874:Immediate-Early Proteins; D050813:Octamer Transcription Factor-2; D010750:Phosphoproteins; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D000099229:RE1-Silencing Transcription Factor; C497325:EGR1 protein, human; C486109:Egr1 protein, mouse; C052130:GAL4 protein, S cerevisiae; C058435:POU2F2 protein, human; C489206:Pou2f2 protein, mouse; C494698:YY1 protein, human; C096823:Zfp90 protein, mouse; C075995:down-regulator of transcription 1; C533424:Hdac2 protein, mouse