Distinct chromatin structures at the monoamine oxidase-A promoter correlate with allele-specific expression in SH-SY5Y cells.
MAOA
VNTR
X chromosome
X inactivation
chromatin
epigenetics
gender
gene expression
mental health
transcription
Journal
Genes, brain, and behavior
ISSN: 1601-183X
Titre abrégé: Genes Brain Behav
Pays: England
ID NLM: 101129617
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
02
11
2017
revised:
19
02
2018
accepted:
13
04
2018
pubmed:
19
4
2018
medline:
10
1
2020
entrez:
19
4
2018
Statut:
ppublish
Résumé
Monoamine oxidase-A (MAOA) metabolises monoamines and is implicated in the pathophysiology of psychiatric disorders. A polymorphic repetitive DNA domain, termed the uVNTR (upstream variable number tandem repeat), located at the promoter of the MAOA gene is a risk factor for many of these disorders. MAOA is on the X chromosome suggesting gender could play a role in regulation. We analysed MAOA regulation in the human female cell line, SH-SY5Y, which is polymorphic for the uVNTR. This heterozygosity allowed us to correlate allele-specific gene expression with allele-specific transcription factor binding and epigenetic marks for MAOA. Gene regulation was analysed under basal conditions and in response to the mood stabiliser sodium valproate. Both alleles were transcriptionally active under basal growth conditions; however, the alleles showed distinct transcription factor binding and epigenetic marks at their respective promoters. Exposure of the cells to sodium valproate resulted in differential allelic expression which correlated with allele-specific changes in distinct transcription factor binding and epigenetic marks at the region encompassing the uVNTR. Biochemically our model for MAOA promoter function has implications for gender differences in gene × environment responses in which the uVNTR has been implicated as a genetic risk.
Identifiants
pubmed: 29667298
doi: 10.1111/gbb.12483
pmc: PMC6617726
doi:
Substances chimiques
Antimanic Agents
0
Chromatin
0
Transcription Factors
0
Valproic Acid
614OI1Z5WI
Monoamine Oxidase
EC 1.4.3.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12483Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400577
Pays : United Kingdom
Informations de copyright
© 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
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