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The imprinted Zdbf2 gene finely tunes hypothalamic control of feeding and growth in neonates.

ABSTRACT: The imprinted Zdbf2 gene finely tunes hypothalamic control of feeding and growth in neonates.

PROVIDER: PRJNA641890 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12091748_1.fastq.gz	Fastqsanger.gz
	SRR12091748_2.fastq.gz	Fastqsanger.gz
	SRR12091749_1.fastq.gz	Fastqsanger.gz
	SRR12091749_2.fastq.gz	Fastqsanger.gz
	SRR12091750_1.fastq.gz	Fastqsanger.gz

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The imprinted Zdbf2 gene finely tunes hypothalamic control of feeding and growth in neonates.

Project description:To allow identification of differentially expressed genes between WT and Zdbf2-KO hypothalamus in mouse pups at 3 and 10dpp, mutants and control RNA-seq were conducted starting from whole hypothalamus RNA.

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The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates.

Project description:Genomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressed Zdbf2 gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found that Zdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half of Zdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain.

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Targeted DNA methylation analysis of the imprinted loci FAM50B and ZDBF2 in a cohort of small for gestational age born children

Project description:In this cohort of 52 individuals born small for gestational age we analyzed the DNA methylation of the two imprinted genes ZDBF2 and FAM50B using CpGs from these loci represented on the Illumina Infinium HumanMethylation450k Bead Chip.This cohort partly overlaps with an already published cohort analyzed for the potential influence of growth hormone therapy on the DNA methylation (GSE57205). Our analysis revealed one individual with a hypermethylation in ZDBF2.

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [bisulfite-seq]

Project description:Early mammalian development is accompanied by a profound global remodeling of chromatin-based regulation. The Zdbf2 locus provides a valuable model to uncover the effect of dynamic chromatin transition, as it is polycomb silenced in embryonic stem cells (ESCs) and only becomes activated after Long isoform of Zdbf2 (Liz) transcription-dependent de novo DNA methylation during differentiation. Here we show that four enhancers contribute to the Liz-to-Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. CTCF plays a key role in partitioning the locus in ESCs, when Liz is active and Zdbf2 is silenced. The partition is relieved when Zdbf2 becomes DNA methylated and active. Mutant ESCs that lack the partition fail to properly activate Zdbf2. Notably, the CTCF-based regulation occurs independently of the polycomb and DNA methylation pathways, suggesting a multi-layered regulatory framework that ensures proper epigenetic programming of a developmentally important gene.

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [ATAC-Seq]

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [4C-Seq]

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [RNA-Seq]

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Methylation status in human sperm

Project description:Genomic imprinting describes the expression of a subset of mammalian genes from one parental chromosome. The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpG-dinucleotides at differentially methylated regions (DMRs) during gametogenesis. We identified the paternally methylated DMR at human chromosome 2 near the imprinted ZDBF2 gene using a methylated-DNA immunoprecipitation-on-chip (meDIP-on-chip) method applied to DNA from sperm. To analyze whether or not the GPR1-ZDBF2 DMR is conserved in human genome, methylation analysis of human sperm sample was performed using MeDIP and genome tiling array.

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Methylation status in AG- and PG-derived cells and sperm

Project description:Genomic imprinting describes the expression of a subset of mammalian genes from one parental chromosome. The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpG-dinucleotides at differentially methylated regions (DMRs) during gametogenesis. We identified the paternally methylated DMRs at mouse chromosome 1 near the imprinted Zdbf2 gene using a methylated-DNA immunoprecipitation-on-chip (meDIP-on-chip) method applied to DNA from parthenogenetic (PG)- and androgenetic (AG)-derived cells and sperm. To identify novel DMRs, genome-wide methylation analysis of three samples were performed using MeDIP and whole genome tiling array.

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