Allelic imbalance is a prevalent and tissue-specific feature of the mouse transcriptome
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Stefan Pinter
PROVIDER: E-GEOD-58524 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:We used a reciprocal crosses model to assess the allelic imbalance in early mouse embryo
2019-11-05 | GSE127106 | GEO
Project description:In order to study parent-of-origin effects on gene expression, we performed RNAseq analysis (100bp single end reads) of 165 children who formed part of mother/father/child trios where genotype data was available from the HapMap and/or 1000 Genomes Projects. Based on phased genotypes at heterozygous SNP positions, we generated allelic counts for expression of the maternal and paternal alleles in each individual. This analysis reveals significant bias in the expression of the parental alleles for dozens of genes, including both previously known and novel imprinted transcripts.
2018-06-15 | GSE92521 | GEO
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression. Input and Zfp57 CHiP-Seq profiles of hybrid Black6/Cast ES cells were generated by sequencing using the Illumina GAIIx platform.
2015-05-08 | E-GEOD-55382 | biostudies-arrayexpress
Project description:Dynamic allelic imbalance in early mouse embryo
| PRJNA524173 | ENA
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression.
2015-05-08 | GSE55382 | 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. 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:Multiple regulatory layers influence allele-specific expression (ASE), particularly through sequence-dependent and parent-of-origin-dependent mechanisms at the transcriptional level. However, little is known about allele-specific gene regulation at the post-transcriptional level. Here, we conduct transcriptome-wide analysis of allele-specific m6A in mice. Using early postnatal cerebellum and cerebrum samples from reciprocal crosses of two divergent mouse strains, we employed quantitative m6A assays to measure allelic differences in m6A at single-base resolution. Our study reveals widespread sequence-dependent allelic imbalance in m6A methylation, identifying thousands of allele-specific m6A (ASm6A) sites with statistically significant and reproducible allelic methylation differences across diverse samples. We find evidence of potential cis-regulatory variants within 50-nt flanking regions of these ASm6A sites, with the highest enrichment at the motif positions. Intriguingly, we detect parental effects on allelic methylation across m6A sites exhibiting parent-of-origin-dependent ASE. For both sequence- and parent-of-origin-dependent allelic m6A methylation, we observe opposing allelic preferences between methylation and expression, suggesting a potential role of ASm6A in regulating ASE through negative effects on gene expression. Overall, our findings reveal that both cis-acting and parent-of-origin effects influence ASm6A, offering new insights into post-transcriptional mechanisms of ASE regulation.
2024-04-26 | GSE265978 | GEO
Project description:Multiple regulatory layers influence allele-specific expression (ASE), particularly through sequence-dependent and parent-of-origin-dependent mechanisms at the transcriptional level. However, little is known about allele-specific gene regulation at the post-transcriptional level. Here, we conduct transcriptome-wide analysis of allele-specific m6A in mice. Using early postnatal cerebellum and cerebrum samples from reciprocal crosses of two divergent mouse strains, we employed quantitative m6A assays to measure allelic differences in m6A at single-base resolution. Our study reveals widespread sequence-dependent allelic imbalance in m6A methylation, identifying thousands of allele-specific m6A (ASm6A) sites with statistically significant and reproducible allelic methylation differences across diverse samples. We find evidence of potential cis-regulatory variants within 50-nt flanking regions of these ASm6A sites, with the highest enrichment at the motif positions. Intriguingly, we detect parental effects on allelic methylation across m6A sites exhibiting parent-of-origin-dependent ASE. For both sequence- and parent-of-origin-dependent allelic m6A methylation, we observe opposing allelic preferences between methylation and expression, suggesting a potential role of ASm6A in regulating ASE through negative effects on gene expression. Overall, our findings reveal that both cis-acting and parent-of-origin effects influence ASm6A, offering new insights into post-transcriptional mechanisms of ASE regulation.
2024-04-26 | GSE265977 | GEO
Project description:Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashion. Following fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci including imprinting control regions. How parental chromatin becomes equalized and how imprinted genes escape this wave of reprogramming is largely unknown. Here we generated high-resolution maps of parental allele-specific DNase I hypersensitive sites (DHSs) in zygotes and morula embryos by using physically-isolated parental pronuclei, as well as parthenogenetic (PG) and androgenetic (AG) embryos. Allelic transcriptome analyses revealed a high correlation between allelic DHSs and allelic gene expression not only in known imprinted genes but also in dozens of genes not previously known to be imprinted. Interestingly, we found that many paternally- expressed genes harbor paternal allele-specific DHSs (Ps-DHSs) that are highly enriched for histone H3K27 tri-methylation (H3K27me3) but devoid of DNA methylation in maternal allele. Importantly, ectopic removal of the H3K27me3 turns Ps-DHSs into bi- allelic DHSs and induces maternal allele derepression in genes that include maternal DNA methylation-independent imprinted genes Gab1, Sfmbt2, Slc38a4, and Phf17 (also known as Jade1). Thus, our study not only reveals parental allele-specific chromatin accessibility of preimplantation embryos, but also identifies maternal H3K27me3 as a DNA methylation- independent mechanism for genomic imprinting.
2017-07-19 | GSE92605 | GEO