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DNA methylation of amino acid transporter genes in the human placenta

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.
0143-4004
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
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, 64-73. (doi:10.1016/j.placenta.2017.10.010).

Record type: Article

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
ORCID for K. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for C. Bell: ORCID iD orcid.org/0000-0003-4601-1242
ORCID for N. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for R. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for J. Cleal: ORCID iD orcid.org/0000-0001-7978-4327

Catalogue record

Date deposited: 07 Dec 2017 17:30
Last modified: 26 Nov 2021 02:48

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Contributors

Author: C. Simner
Author: B. Novakovic
Author: K. Lillycrop ORCID iD
Author: C. Bell ORCID iD
Author: N. Harvey ORCID iD
Author: C. Cooper ORCID iD
Author: R. Saffery
Author: R. Lewis ORCID iD
Author: J. Cleal ORCID iD

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