Transcriptional 'silencer' element in rat repetitive sequences associated with the rat insulin 1 gene locus

L. Laimins, M. Holmgren-Konig, G. Khoury

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Abstract

The enhancer elements from either simian virus 40 or murine sarcoma virus activate the expression of a transfected rat insulin 1 (rI1) gene when placed within 2.0 kilobases or less of the rI1 gene cap site. Inclusion of 4.0 kilobases of upstream rI1 sequence, however, results in a substantial reduction in the enhancer-dependent insulin gene expression. These observations suggested that a negative transcriptional regulatory element was present between 2.0 and 4.0 kilobases of the rI1 sequence. To test this notion, we employed a heterologous enhancer-dependent transcription assay in which the simian virus 40 72-base-pair repeat is linked to a human β-globin gene. Addition of the upstream rI1 element to this system decreased the level of enhancer-dependent β-globin transcription by a factor of 5 to 15. This rI1 'silencer' element functions in a manner relatively independent of position and orientation and requires a cis-dependent relationship to the transcription unit on which it acts. Thus, the silencer sequences seems to have a number of the characteristics of enhancer elements, and we suggest that it may function by the converse of the enhancer mechanism. The rI1 silencer sequence was identified as a member of a long interspersed rat repetitive family. Thus, a potential role for certain repetitive sequences interspersed throughout the eukaryotic genome may be to regulate gene expression by retaining transcriptional activity within defined domains.

Original languageEnglish (US)
Pages (from-to)3151-3155
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number10
DOIs
StatePublished - Jan 1 1986

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