A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57
Abstract Background Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of foli...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Clinical Epigenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13148-019-0618-0 |
| _version_ | 1818583782059409408 |
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| author | Rachelle E. Irwin Sara-Jayne Thursby Miroslava Ondičová Kristina Pentieva Helene McNulty Rebecca C. Richmond Aoife Caffrey Diane J. Lees-Murdock Marian McLaughlin Tony Cassidy Matthew Suderman Caroline L. Relton Colum P. Walsh |
| author_facet | Rachelle E. Irwin Sara-Jayne Thursby Miroslava Ondičová Kristina Pentieva Helene McNulty Rebecca C. Richmond Aoife Caffrey Diane J. Lees-Murdock Marian McLaughlin Tony Cassidy Matthew Suderman Caroline L. Relton Colum P. Walsh |
| author_sort | Rachelle E. Irwin |
| collection | DOAJ |
| description | Abstract Background Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86). Results The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels. Conclusions These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787. |
| first_indexed | 2024-12-16T08:10:45Z |
| format | Article |
| id | doaj.art-05ddd67e99ae42e5a441411b9bca5440 |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-16T08:10:45Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-05ddd67e99ae42e5a441411b9bca54402022-12-21T22:38:20ZengBMCClinical Epigenetics1868-70751868-70832019-02-0111111610.1186/s13148-019-0618-0A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57Rachelle E. Irwin0Sara-Jayne Thursby1Miroslava Ondičová2Kristina Pentieva3Helene McNulty4Rebecca C. Richmond5Aoife Caffrey6Diane J. Lees-Murdock7Marian McLaughlin8Tony Cassidy9Matthew Suderman10Caroline L. Relton11Colum P. Walsh12Genomic Medicine Research Group, School of Biomedical Sciences, Ulster UniversityGenomic Medicine Research Group, School of Biomedical Sciences, Ulster UniversityGenomic Medicine Research Group, School of Biomedical Sciences, Ulster UniversityNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster UniversityNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster UniversityMRC Integrative Epidemiology Unit, Bristol Medical School, University of BristolNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster UniversityGenomic Medicine Research Group, School of Biomedical Sciences, Ulster UniversityPsychology Institute, Ulster UniversityPsychology Institute, Ulster UniversityMRC Integrative Epidemiology Unit, Bristol Medical School, University of BristolMRC Integrative Epidemiology Unit, Bristol Medical School, University of BristolGenomic Medicine Research Group, School of Biomedical Sciences, Ulster UniversityAbstract Background Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86). Results The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels. Conclusions These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.http://link.springer.com/article/10.1186/s13148-019-0618-0Folic acidDNA methylationCord bloodOffspringImprintingZFP57 |
| spellingShingle | Rachelle E. Irwin Sara-Jayne Thursby Miroslava Ondičová Kristina Pentieva Helene McNulty Rebecca C. Richmond Aoife Caffrey Diane J. Lees-Murdock Marian McLaughlin Tony Cassidy Matthew Suderman Caroline L. Relton Colum P. Walsh A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 Clinical Epigenetics Folic acid DNA methylation Cord blood Offspring Imprinting ZFP57 |
| title | A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 |
| title_full | A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 |
| title_fullStr | A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 |
| title_full_unstemmed | A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 |
| title_short | A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57 |
| title_sort | randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation regulated control element at zfp57 |
| topic | Folic acid DNA methylation Cord blood Offspring Imprinting ZFP57 |
| url | http://link.springer.com/article/10.1186/s13148-019-0618-0 |
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