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A bi-functional activator/repressor element required for transcriptional activity of the human UCH-L1 gene assembles a neuron-specific protein: single-strand DNA complex

Lookup NU author(s): Professor Derek Mann

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Abstract

The ubiquitin C-terminal hydrolase (UCH)-L1 gene is expressed in a tissue- and cell-specific manner with expression restricted to neurons and neuroendocrine cells. Regulatory DNA sequences from the 5' untranscribed region of the human UCH-L1 gene will promote neuron specific transcription providing that a 59 bp sequence located between nucleotides -182 and -123 is present in reporter gene constructs. We show that this 59 bp sequence is a bi-functional regulator of transcription, acting as an activator in human neuroblastoma cells (SH-SY5Y) and a strong repressor in HeLa cells. The sense strand of the UCH-L1 activator/repressor element can interact with nuclear proteins that recognize single stranded DNA in a sequence specific manner. Nuclear extracts from neuroblastoma cells generate a protein:ssDNA interaction called complex 1B could be converted into a lower mobility complex (1A) by increasing the protein:DNA ratio. This conversion was not observed when using nuclear extracts from HeLa cells. Formation of neuron specific complex 1A could be prevented by incubation of protein:ssDNA complexes at 2 degrees C or in the presence of mM concentrations of MgCl2. In conclusion, we have identified a novel bi-functional regulatory DNA element in the promoter of the human UCH-L1 gene that contributes to neuron-restricted transcription and which can assemble a neuron specific protein:ssDNA complex on its sense strand.

Publication metadata

Author(s): Mann DA; Trowern AR

Publication type: Article

Publication status: Published

Journal: Neuroscience Letters

Year: 1999

Volume: 272

Issue: 1

Pages: 25-8

Print publication date: 01/09/2003

ISSN (print): 0304-3940

ISSN (electronic): 1872-7972

Publisher: Elsevier Science Ireland Ltd

URL: http://dx.doi.org/10.1016/S0304-3940(99)00479-6

DOI: 10.1016/S0304-3940(99)00479-6

Notes: 0304-3940 (Print) Journal Article

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