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Random monoallelic gene expresson in ESC and NPC from C57BL6xCAST hybrid

ABSTRACT: Random monoallelic gene expresson in ESC and NPC from C57BL6xCAST hybrid

PROVIDER: PRJEB5697 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR440421_1.fastq.gz	Fastqsanger.gz
	ERR440421_2.fastq.gz	Fastqsanger.gz
	ERR440422_1.fastq.gz	Fastqsanger.gz
	ERR440422_2.fastq.gz	Fastqsanger.gz
	ERR440423_1.fastq.gz	Fastqsanger.gz

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Random monoallelic gene expresson in ESC and NPC from C57BL6xCAST hybrid

Project description:The goal of this experiment is to identify autosomal random monoallelic gene in ESC and NPC from a C57BL6J x CAST hybrid

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SNP array in NPC and ESC from C57BL6xCAST hybrid

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The developmental dynamics and disease potential of random monoallelic gene expression

Project description:X-chromosome inactivation (XCI) in females and allelic exclusion of olfactory receptor or immunoglobulin loci, represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation and once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism, similarly to XCI. Several of the genes identified play important roles in development and have also been implicated in human autosomal dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control and in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease. The hybrid mouse ES cell lines F1-21.6 and F1-23 (129Sv-Cast/EiJ), previously described in (Luikenhuis et al., 2001) and (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared from the mouse ES cell lines, 4 NPC clones derived from ES cell line F1-21.6 plus one replicate, and 4 NPC clones derived from ES cell line F1-23 plus one replicate. Library preparation after polyadenylated RNA purification was performed according to the standard Illumina instructions. Paired-end 100bp reads were generated using the HiSeq 2000 sequencing platform.

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Random monoallelic expression in the mouse: SNP array data

Project description:Random monoallelic expression is defined by the allele-specific expression of genes, and by the fact that for an individual cell this monoallelic expression is neither obligate nor necessarily coordinated with the allelic expression in other cells. In order to find novel examples of random monoallelic expression in mouse, we did a transcriptome-wide survey of allele-specific gene expression in two different immortalized cell types. Lymphoblast cell lines and fibroblast cell lines were established (both clonal and nonclonal) and were used as a source of both nuclear RNA and genomic DNA. These samples were assessed for allele-specific gene expression using a custom-designed Mouse SNP Chip. A large number of genes (over 10% of those that were assessed in lymphoblast clones) displayed random monoallelic expression.

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Deconstructing lincRNA regulation during ESC to NPC differentiation

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Binary outcomes of enhancer activity underlie stable random monoallelic expression

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PRC2 profile and chromatin marks in ESC and NPC

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Binary outcomes of enhancer activity underlie stable random monoallelic expression

Project description:We analyzed the natural killer (NK) cell receptor genes as in vivo genetic model to study random monoallelic gene expression (RME). These genes are expressed randomly, and largely monoallelically, in subsets of NK cells to generate a repertoire of specificities. We found that enhancers directly controlled the probability of expression of both RME and related, broadly expressed genes. We present an analysis of the accessibility (ATAC-seq) and both active and repressive histone modifications of elements associated with both expressed and silent alleles of the NK receptor genes in primary cells. The goals of this study were to assess the chromatin state of the silent and active alleles of the monoallelically expressed natural killer (NK) cell receptor genes.

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