A randomised controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57
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PROVIDER: PRJNA735771 | ENA |
REPOSITORIES: ENA
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Project description: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. Ethics approval and consent to participate: The Office for Research and Ethics Committees Northern Ireland (ORECNI) granted ethical approval (reference 05/ Q2008/21) and each participant gave written informed consent upon recruitment.
2021-06-08 | GSE176325 | GEO
Project description:BackgroundMaternal 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).ResultsThe 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.ConclusionsThese 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.
| S-EPMC6380035 | biostudies-literature
Project description:We have performed ChIP seq analysis to obtain the positions of KAP1 and ZFP57 binding sites in mouse ES cells. By comparing the two lists, we were able to find bona fide sites. ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells
2011-11-07 | E-GEOD-31181 | biostudies-arrayexpress
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression. Input and Zfp57 CHiP-Seq profiles of hybrid Black6/Cast ES cells were generated by sequencing using the Illumina GAIIx platform.
2015-05-08 | E-GEOD-55382 | biostudies-arrayexpress
Project description:Caco-2, HT29, CCD841CoTr exposed to 10ng/mL, 100ng/mL and 4000ng/mL folic acid
2010-06-10 | E-GEOD-2047 | biostudies-arrayexpress
Project description:Caco-2, HT29, CCD841CoTr exposed to 10ng/mL, 100ng/mL and 4000ng/mL folic acid Keywords: dose response
2005-05-08 | GSE2047 | GEO
Project description:We did RNA-seq analysis to compare gene expression profiles in mouse embryos with or without ZFP57. We also perfromed whole-genome bisulfite sequencing analysis (WGBS) for the Zfp57 mutant mouse embryos and control heterozygous embryos. We analyzed DNA methylation at the imprinting control regions (ICRs), differentially methylation regions (DMRs) and repetitive elements including LINE-1, LINE-2, SINE, LTR and IAP.
2021-01-27 | GSE165079 | GEO
Project description:RNA-seq analysis was used to find the target genes of Zfp57 in mouse embryos.
2022-03-10 | GSE189761 | GEO
Project description:RNA-seq and expression profile of WT and ZFP57 KO ES cells RNA was extracted from both cell lines, PolyA RNA were extracted and RNA-seq was performed
2011-11-07 | E-GEOD-31182 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE31181: ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells GSE31182: RNA-seq and expression profile of WT and ZFP57 KO ES cells Refer to individual Series
2011-11-07 | E-GEOD-31183 | biostudies-arrayexpress