Characterisation of multiple regulatory domains spanning the major transcriptional start site of the FUS gene, a candidate gene for motor neurone disease

Khursheed, Kejhal ORCID: 0000-0002-3778-1643, Wilm, Thomas, Cashman, Christine, Quinn, John ORCID: 0000-0003-3551-7803, Bubb, Vivien ORCID: 0000-0003-2763-7004 and Moss, Diana (2015) Characterisation of multiple regulatory domains spanning the major transcriptional start site of the FUS gene, a candidate gene for motor neurone disease. Brain Research, 1595. pp. 1-9.

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Abstract

Fused-In-Sarcoma (FUS) is a candidate gene for neurological disorders including motor neurone disease and Parkinson’s disease in addition to various types of cancer. Recently it has been reported that over expression of FUS causes motor neurone disease in mouse models hence mutations leading to changes in gene expression may contribute to the development of neurodegenerative disease. Genome evolutionary conservation was used to predict important cis-acting DNA regulators of the FUS gene promoter that direct transcription. The putative regulators identified were analysed in reporter gene assays in cells and in chick embryos. Our analysis indicated in addition to regulatory domains 5’ of the transcriptional start site an important regulatory domain resides in intron 1 of the gene itself. This intronic domain functioned both in cell lines and in vivo in the neural tube of the chick embryo including developing motor neurones. Our data suggests the interaction of multiple domains including intronic domains are involved in expression of FUS. A better understanding of the regulation of expression of FUS may give insight into how its stimulus inducible expression may be associated with neurological disorders.

Item Type:	Article
Uncontrolled Keywords:	evolutionary conserved domains, reporter gene assays, chick embryon model, ALS, Parkinson's disease, FTD
Subjects:	?? Q1 ??
Depositing User:	Symplectic Admin
Date Deposited:	14 Jan 2015 11:52
Last Modified:	15 Dec 2022 12:13
DOI:	10.1016/j.brainres.2014.10.056
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2005001