Dynamic allelic imbalance in early mouse embryo
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ABSTRACT:
PROVIDER: PRJNA524173 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We used a reciprocal crosses model to assess the allelic imbalance in early mouse embryo
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Project description:Enhancer RNAs (eRNAs) play critical roles in diverse biological processes by mediating the activation of their target genes. However, the systematic landscape and potential regulations and functions of eRNAs during mammalian early embryo development remains elusive. Here, we present the comprehensive detection and characterization of eRNAs during mouse early embryo development. We demonstrated the spatiotemporal and allelic landscape of eRNA expression. We found the asymmetric activation of paternal-specific eRNAs during zygotic genome activation (ZGA). We identified TFs and their cooperation in regulating dynamic eRNA expression. eRNA are involved in multiple developmental signaling pathways through putatively regulating their target genes. Interestingly, we observed that the transcriptions of enhancers themselves are also widely modulated by eRNAs during mouse early embryo development. Critically, we de novo identified a novel eRNA transcribed from a super-enhancer region exclusively expressed at 2-cell stage of mouse early embryos and experimentally validated its key functional role in regulating ZGA and early embryo development.
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Project description:We perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ~20% of the mouse transcriptome. Allelic imbalance attributed to genotype is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5’ and 3’ termini of transcripts. We further identify novel random monoallelic and imprinted genes, and find that genotype can compete with parental origin even in the setting of large imprinted regions. PolyA-selected RNA-sequencing in F1 hybrid and parental cells of Mm. musculus and Mm. castaneus origin
2015-05-28 | E-GEOD-58524 | biostudies-arrayexpress
Project description:The diploid fungal pathogen Candida albicans is a highly heterozygous organism, with numerous non-synonymous substitutions often seen within two alleles. RNA-sequencing of the wild-type strain SC5314 has revealed 233 genes with significant levels of allelic expression imbalance. Overall percentage protein identity comparisons were significantly lower in these differentially expressed alleles. This suggests that two different, perhaps functionally divergent, proteins are being expressed at significantly different quantities by the two alleles of a single gene. Previously, gene expression levels have been correlated with structural factors such as GC content, ORF length and codon usage. Here, these factors were first correlated with overall gene expression data to decipher the relationship they have with gene expression in Candida albicans. These relationships were then used to assess the contribution of these factors to allelic expression imbalance. GC content and codon usage did not differ significantly in differentially expressed alleles whereas ORF length was found to be significantly lower in the allele with lowest expression. This surprising result goes against the overall trend observed between length and gene expression. Differences in GC content and ORF length between alleles correlated strongly with percentage protein identity, suggesting an indirect link between these factors and allelic expression imbalance. One sample (SC5314: wild-type strain) assessed in triplicate and compared to the reference diploid genome
2014-06-30 | E-GEOD-35233 | biostudies-arrayexpress
Project description:We perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ~20% of the mouse transcriptome. Allelic imbalance attributed to genotype is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5’ and 3’ termini of transcripts. We further identify novel random monoallelic and imprinted genes, and find that genotype can compete with parental origin even in the setting of large imprinted regions.
2015-05-28 | GSE58524 | GEO
Project description:The diploid fungal pathogen Candida albicans is a highly heterozygous organism, with numerous non-synonymous substitutions often seen within two alleles. RNA-sequencing of the wild-type strain SC5314 has revealed 233 genes with significant levels of allelic expression imbalance. Overall percentage protein identity comparisons were significantly lower in these differentially expressed alleles. This suggests that two different, perhaps functionally divergent, proteins are being expressed at significantly different quantities by the two alleles of a single gene. Previously, gene expression levels have been correlated with structural factors such as GC content, ORF length and codon usage. Here, these factors were first correlated with overall gene expression data to decipher the relationship they have with gene expression in Candida albicans. These relationships were then used to assess the contribution of these factors to allelic expression imbalance. GC content and codon usage did not differ significantly in differentially expressed alleles whereas ORF length was found to be significantly lower in the allele with lowest expression. This surprising result goes against the overall trend observed between length and gene expression. Differences in GC content and ORF length between alleles correlated strongly with percentage protein identity, suggesting an indirect link between these factors and allelic expression imbalance.
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Project description:DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair.
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