Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Mayes, M.B., Morgan, T., Winston, J., Buxton, D.S., Kamat, M.A., Smith, D., Williams, M., Martin, R.L., Kleinjan, D.A., Cooper, D.N., Upadhyaya, M. and Chuzhanova, N. ORCID: 0000-0002-4655-3618, 2015. Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD. Human Genomics, 9. ISSN 1479-7364

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Abstract

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers.

Item Type:	Journal article
Publication Title:	Human Genomics
Creators:	Mayes, M.B., Morgan, T., Winston, J., Buxton, D.S., Kamat, M.A., Smith, D., Williams, M., Martin, R.L., Kleinjan, D.A., Cooper, D.N., Upadhyaya, M. and Chuzhanova, N.
Publisher:	BioMed Central Ltd.
Place of Publication:	London
Date:	2015
Volume:	9
ISSN:	1479-7364
Identifiers:	Number Type 10.1186/s40246-015-0047-x DOI
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	28 Oct 2015 10:33
Last Modified:	09 Jun 2017 13:55
URI:	https://irep.ntu.ac.uk/id/eprint/25847

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