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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [ChIP-seq]

ABSTRACT: To investigate the associated with DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.

ORGANISM(S): Mus musculus

PROVIDER: GSE204869 | GEO | 2022/09/20

REPOSITORIES: GEO

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [hMeDIP]

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Project description:To investigate the associated with the levels of DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated. We then performed gene expression profiling analysis using data obtained from RNA-seq of the cell model.

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Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects

Project description:Neural tube defects (NTDs) are one of the most severe congenital abnormalities. Maternal folate deficiency could impact the occurrence of NTDs. Histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects

Project description:Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [MeDIP]

Project description:Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [MeDIP]

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [hMeDIP]

Project description:Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [hMeDIP]

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [ChIP-seq]

Project description:Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [ChIP-seq]

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Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [RNA-seq]

Project description:Abnormal Transcriptome-wide of DNA demethylation in Folate deficiency caused neural tube defects [RNA-seq]

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Efficient induction of Gcm1 under folate deficiency promotes vertebrate neural development by Wnt/β-catenin pathway activation

Project description:Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway leads to defective anteroposterior patterning, resulting in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We report here that in C57BL/6C mouse embryonic stem cells (mESC), folate deficiency activates Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promotes the formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex to regulate the Wnt target gene transactivation through the Wnt-responsive elements. Moreover, the enhanced transcriptional activity of Gcm1 is found to be dependent on CREB binding protein. Lastly, in NTDs mouse models and low folate NTDs human brain samples, Gcm1 and Wnt/β-catenin target genes related to neural tube closure are specifically overexpressed. These results indicate that low folate promotes Wnt/β-catenin signaling via activating Gcm1, leading to aberrant vertebrate neural development

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