DNA methylation of amino acid transporter genes in the human placenta
DNA methylation of amino acid transporter genes in the human placenta
Introduction
Placental transfer of amino acids via amino acid transporters is essential for fetal growth. Little is known about the epigenetic regulation of amino acid transporters in placenta. This study investigates the DNA methylation status of amino acid transporters and their expression across gestation in human placenta.
Methods
BeWo cells were treated with 5-aza-2′-deoxycytidine to inhibit methylation and assess the effects on amino acid transporter gene expression. The DNA methylation levels of amino acid transporter genes in human placenta were determined across gestation using DNA methylation array data. Placental amino acid transporter gene expression across gestation was also analysed using data from publically available Gene Expression Omnibus data sets. The expression levels of these transporters at term were established using RNA sequencing data.
Results
Inhibition of DNA methylation in BeWo cells demonstrated that expression of specific amino acid transporters can be inversely associated with DNA methylation. Amino acid transporters expressed in term placenta generally showed low levels of promoter DNA methylation. Transporters with little or no expression in term placenta tended to be more highly methylated at gene promoter regions. The transporter genes SLC1A2, SLC1A3, SLC1A4, SLC7A5, SLC7A11 and SLC7A10 had significant changes in enhancer DNA methylation across gestation, as well as gene expression changes across gestation.
Conclusion
This study implicates DNA methylation in the regulation of amino acid transporter gene expression. However, in human placenta, DNA methylation of these genes remains low across gestation and does not always play an obvious role in regulating gene expression, despite clear evidence for differential expression as gestation proceeds.
64-73
Simner, C.
a06911e9-ad54-4519-98fa-188b8bf538dc
Novakovic, B.
4c418a4c-a521-40ac-a789-ecce9f00532e
Lillycrop, K.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Bell, C.
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Harvey, N.
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Saffery, R.
ed0e44b1-7935-4be9-a37d-1e2936c49ce1
Lewis, R.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Cleal, J.
18cfd2c1-bd86-4a13-b38f-c321af56da66
December 2017
Simner, C.
a06911e9-ad54-4519-98fa-188b8bf538dc
Novakovic, B.
4c418a4c-a521-40ac-a789-ecce9f00532e
Lillycrop, K.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Bell, C.
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Harvey, N.
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Saffery, R.
ed0e44b1-7935-4be9-a37d-1e2936c49ce1
Lewis, R.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Cleal, J.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Simner, C., Novakovic, B., Lillycrop, K., Bell, C., Harvey, N., Cooper, C., Saffery, R., Lewis, R. and Cleal, J.
(2017)
DNA methylation of amino acid transporter genes in the human placenta.
Placenta, 60, .
(doi:10.1016/j.placenta.2017.10.010).
Abstract
Introduction
Placental transfer of amino acids via amino acid transporters is essential for fetal growth. Little is known about the epigenetic regulation of amino acid transporters in placenta. This study investigates the DNA methylation status of amino acid transporters and their expression across gestation in human placenta.
Methods
BeWo cells were treated with 5-aza-2′-deoxycytidine to inhibit methylation and assess the effects on amino acid transporter gene expression. The DNA methylation levels of amino acid transporter genes in human placenta were determined across gestation using DNA methylation array data. Placental amino acid transporter gene expression across gestation was also analysed using data from publically available Gene Expression Omnibus data sets. The expression levels of these transporters at term were established using RNA sequencing data.
Results
Inhibition of DNA methylation in BeWo cells demonstrated that expression of specific amino acid transporters can be inversely associated with DNA methylation. Amino acid transporters expressed in term placenta generally showed low levels of promoter DNA methylation. Transporters with little or no expression in term placenta tended to be more highly methylated at gene promoter regions. The transporter genes SLC1A2, SLC1A3, SLC1A4, SLC7A5, SLC7A11 and SLC7A10 had significant changes in enhancer DNA methylation across gestation, as well as gene expression changes across gestation.
Conclusion
This study implicates DNA methylation in the regulation of amino acid transporter gene expression. However, in human placenta, DNA methylation of these genes remains low across gestation and does not always play an obvious role in regulating gene expression, despite clear evidence for differential expression as gestation proceeds.
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More information
Accepted/In Press date: 30 October 2017
e-pub ahead of print date: 31 October 2017
Published date: December 2017
Identifiers
Local EPrints ID: 416190
URI: http://eprints.soton.ac.uk/id/eprint/416190
ISSN: 0143-4004
PURE UUID: 14de0bb2-216d-4078-953f-a72a912ad45c
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Date deposited: 07 Dec 2017 17:30
Last modified: 18 Mar 2024 02:58
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Contributors
Author:
C. Simner
Author:
B. Novakovic
Author:
C. Bell
Author:
R. Saffery
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