PXD014088

PXD014088 is an original dataset announced via ProteomeXchange.

Title	EMSY expression affects multiple components of skin barrier with relevance to atopic dermatitis
Description	Atopic dermatitis (AD) is a heritable inflammatory disease, characterised by skin barrier dysfunction. Genome-wide association studies (GWAS) have identified molecular targets with relevance for drug development, but the strongest genetic association, FLG, has not yet been successfully targeted in atopic disease. An AD-associated locus on chromosome 11q13.5 lies between two genes - EMSY and LRRC32 - but the functional mechanisms leading to AD are unclear. We applied a combination of genomic and molecular analytical techniques followed up in patient biopsies, to investigate pathomechanisms at this GWAS locus. Chromosome conformation capture data in keratinocytes shows interaction of the intergenic region in threedimensional space with EMSY. siRNA-mediated knockdown of EMSY in skin organoid culture leads to enhanced development of barrier function, measured by water evaporation and dye penetration. Global proteomic analysis of skin organoids with EMSY knockdown shows increased expression of structural and functional proteins, confirmed by histological and ultrastructural features. Lipid analysis shows an increase in ceramides known to be reduced in AD. Conversely, over-expression of EMSY in primary human keratinocytes leads to a reduction in biomarkers of barrier formation. Finally, skin biopsy samples from patients with AD show greater EMSY staining in the nucleus, consistent with increased functional effect of this DNAbinding protein. Together our findings demonstrate an important role for EMSY in transcriptional regulation and skin barrier formation, supporting EMSY inhibition as a therapeutic approach for AD.
HostingRepository	PRIDE
AnnounceDate	2019-06-24
AnnouncementXML	Submission_2019-06-27_02:01:12.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara ten Have
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-31 06:11:12	ID requested
1	2019-06-24 07:21:32	announced
⏵ 2	2019-06-27 02:01:13	announced	Updated publication reference for PubMed record(s): 31158401.

Elias MS, Wright SC, Remenyi J, Abbott JC, Bray SE, Cole C, Edwards S, Gierlinski M, Glok M, McGrath JA, Nicholson WV, Paternoster L, Prescott AR, Have ST, Whitfield PD, Lamond AI, Brown SJ, EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis. J Allergy Clin Immunol, 144(2):470-481(2019) [pubmed]

submitter keyword: Human, Skin, Proteomics, organotypic culture

Sara Brown
contact affiliation	Skin Research Group, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, Scotland, UK.
contact email	s.j.brown@dundee.ac.uk
lab head
Sara ten Have
contact affiliation	The Centre for Gene Regulation and Expression
contact email	s.m.tenhave@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014088
     1. Label: PRIDE project
     2. Name: EMSY expression affects multiple components of skin barrier with relevance to atopic dermatitis