Project description:N6-methyladenosine (m6A) is the most common internal modification in eukaryotic messenger RNAs (mRNAs) and plays essential roles in mammals. The function of this chemical modification is deciphered by m6A-specific binding proteins of the YTH family. Recent studies indicated that m6A methyltransferase METTL3 ('writer') and demethylase FTO ('eraser') play critical roles in cardiovascular diseases. However, function of m6A 'reader' proteins in the heart is still largely unknown. Here, we report that cardiac-speciﬁc ablation of Ythdc1 in postnatal heart exhibits progressive dilated cardiomyopathy, heart failure and dramatically increases the incidence of postnatal lethality. Mechanically, the transcript of Titin-the major DCM and heart failure related gene-is decorated by m6A modification and directly recognized by YTHDC1, deficiency of Ythdc1 in heart results in abnormal splicing of TTN and disarray of sarcomeric structures in the cardiomyocytes subsequently. Collectively, we demonstrated that YTHDC1-dependent TTN splicing is crucial for the postnatal heart development and cardiac function, which probably provides a potential target for treating DCM through tuning m6A modification of TTN mRNA.

2022-08-01 | GSE164353 | GEO

YTHDC1 is essential for cardiac development

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-05 | GSE241272 | GEO

ATAC-seq of gata5GFP+/- cells in WT and Gata5/6 deficient zebrafish embryos during gastrulation

Project description:Gata5/6 are essential regulators in zebrafish heart development. To understand how Gata5/6 affects the chromatin accessibility and regulates cardiac gene expression, we FACS-isolated GFP+ and GFP- cells from Tg(gata5:GFP) transgenic embryos in both control and Gata5/6 deficient embryos (injected with Gata5/6 morpholinos) and conducted ATAC-seq. We performed the experiments at 8 hours post fertilization, intending to dissect the role of Gata5/6 in the earliest step in cardiac lineage specification. We did 2-3 biological replicates for each sample. ATAC-seq libraries were made using previously published protocol (Buenrostro et al., Nat. Methods, 2013. DOI: 10.1038/nmeth.2688) and sequenced on Illumina Hiseq2500.

2021-12-31 | E-MTAB-10427 | biostudies-arrayexpress

Nr5a2 is dispensable for ZGA but essential for morula development [ATAC-seq]

Project description:Nr5a2 is dispensable for ZGA but essential for morula development [ATAC-seq]

| PRJNA1111798 | ENA

RNA N6-methyladenosine reader YTHDC1 is essential for TGF-beta-mediated metastasis of triple negative breast cancer [m6A-Seq]

Project description:RNA N6-methyladenosine (m6A) modification and its regulators fine tune gene expression and contribute to tumorigenesis. Here, we uncover the oncogenic role and mechanism of YTHDC1, an m6A reader positively correlated to poor prognosis in breast cancer patients. In a mammary fat pad mouse model, YTHDC1 significantly promoted lung metastasis of triple negative breast cancer (TNBC) cells. Using transcriptome-wide sequencing techniques, we found dysregulation of metastasis-related pathways following YTHDC1 depletion and demonstrated that YTHDC1 is critical for nuclear export of SMAD3 mRNA. YTHDC1 depletion desensitizes TNBC cells to TGF-β, resulting in impaired TGF-β-induced gene signature and inhibition on epithelial-mesenchymal transition (EMT) and cell migration/invasion, which could be at least partially restored by SMAD3 overexpression. Furthermore, we show that the ability of YTHDC1 to recognize m6A on SMAD3 RNA is important for its oncogenic role. Collectively, our study unravels YTHDC1 as vital for distant TNBC metastasis by promoting TGF-β-mediated EMT via SMAD3.

2023-03-25 | GSE193155 | GEO

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