Chromatin signature identifies monoallelic gene expression across mammalian cell types (RNA-seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67379 | GEO | 2015/06/17
SECONDARY ACCESSION(S): PRJNA279688
REPOSITORIES: GEO
Similar Datasets
Project description:Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity.
2015-06-17 | GSE67380 | GEO
Project description:Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. Chromatin immunoprecipitation with antibodies specific for histone modifications H3K27me3 and H3K36me3 and subsequent high-throughput sequencing were performed on fixed chromatin from a B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus.
2015-06-17 | E-GEOD-67380 | biostudies-arrayexpress
Project description:Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. PolyA RNA purification and subsequent high-throughput sequencing were performed on two independent B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus, and on two independent fibroblast clonal cell lines, derived from 129S1/Sv x CAST/EiJ F1 and immortalized with SV40.
2015-06-17 | E-GEOD-67379 | biostudies-arrayexpress
Project description:In mammalian cells, large groups of genes show epigenetically controlled unequal transcription of maternal and paternal alleles. Thousands of autosomal genes subject to monoallelic expression (MAE) comprise the largest such group. The initial random allelic choice in these loci is followed by mitotically stable transmission of the allele-specific state, leading to stable epigenetic and functional differences between clonal cell lineages. Molecular mechanisms underpinning MAE maintenance are not known. We devised and performed a drug screen for reactivation of epigenetically silenced alleles in mouse cells, using a new strategy based on deep targeted allele-specific RNA sequencing, which can read out multiple loci simultaneously. We found that, contrary to previous observations, DNA methylation plays a key role in mitotic memory of MAE in multiple autosomal loci. Having established that a specific perturbation can affect multiple loci, we assessed genome-wide impact of the drug exposure in several clonal cell lines, identifying over 600 genes with allele-specific expression changing with DNA methylation. We found that multiple distinct states of allele-specific expression correspond to the extent of DNA methylation and can be stably maintained, indicating allelic rheostat role of DNA methylation. Our findings reveal a previously unappreciated interplay of genetic and epigenetic control of allele-specific expression and reinforce the role of such regulation in maintaining differences between developmentally equivalent clonal cell lineages.
2023-09-20 | GSE144006 | GEO
Project description:In mammalian cells, large groups of genes show epigenetically controlled unequal transcription of maternal and paternal alleles. Thousands of autosomal genes subject to monoallelic expression (MAE) comprise the largest such group. The initial random allelic choice in these loci is followed by mitotically stable transmission of the allele-specific state, leading to stable epigenetic and functional differences between clonal cell lineages. Molecular mechanisms underpinning MAE maintenance are not known. We devised and performed a drug screen for reactivation of epigenetically silenced alleles in mouse cells, using a new strategy based on deep targeted allele-specific RNA sequencing, which can read out multiple loci simultaneously. We found that, contrary to previous observations, DNA methylation plays a key role in mitotic memory of MAE in multiple autosomal loci. Having established that a specific perturbation can affect multiple loci, we assessed genome-wide impact of the drug exposure in several clonal cell lines, identifying over 600 genes with allele-specific expression changing with DNA methylation. We found that multiple distinct states of allele-specific expression correspond to the extent of DNA methylation and can be stably maintained, indicating allelic rheostat role of DNA methylation. Our findings reveal a previously unappreciated interplay of genetic and epigenetic control of allele-specific expression and reinforce the role of such regulation in maintaining differences between developmentally equivalent clonal cell lineages.
2022-10-06 | GSE144007 | GEO
Project description:Analysis of Allelic bias in clonal lymphoblastoid cells. Abstract: In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ~20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation.
2013-12-31 | GSE52090 | GEO
Project description:Analysis of Allelic bias in clonal lymphoblastoid cells. Abstract: In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ~20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. Poly A purified total RNA was used for library construction using a method described by Parkhomchuk et. al. NAR 2009. The library was strand-specific but the pipeline for data analysis does not assume the library is strand-specific.
2013-12-31 | E-GEOD-52090 | biostudies-arrayexpress
Project description:Nanoparticles (NPs) are engineered in the nanoscale (<100nm) to have unique physico-chemical properties from their bulk counterparts. Nanosilver (nAg) is the most prevalent nanoparticle in consumer products due to its strong antimicrobial action. While nAg toxicity at high concentrations has been well described, the sublethal effects at or below regulatory guidelines are relatively unknown. Amphibian metamorphosis is mediated by thyroid hormone (TH), and initial studies indicate that low concentrations of nAg disrupt TH-dependent responses in precociously induced premetamorphic bullfrog (Rana catesbeiana) tadpoles. The present study examined the effects of environmentally-relevant nAg concentrations (LoAg, 0.018 µg/L; MedAg, 0.18 µg/L; HiAg, 1.8 µg/L) on naturally metamorphosing Xenopus laevis tadpoles in two 28-day chronic exposures beginning with pre- and prometamorphic stages, respectively. nAg was found to significantly bioaccumulate in tadpoles after 28 days. While nAg didn’t alter metamorphic timing, it increased hindlimb length during early premetamorphosis and in post-metamorphic juvenile tadpoles. Using MAGEX microarray and QPCR transcript analyses, 7 markers of nAg exposure were discovered and validated, 5 of which showed nAg-induced disruption of their TH-response. The increased mRNA abundance of two peroxidase genes suggests that nAg could generate reactive oxygen species (ROS) even at low, environmental concentrations. Furthermore, differential responsiveness to nAg was observed between developmental stages. Therefore, low concentrations of nAg had endocrine disruptive effects at both the physiological and molecular level, indicating that regulatory guidelines for silver may need revision.
2016-12-23 | GSE56012 | GEO
Project description:15N-labeled N-acetylglucosamine (NAG) fed to B. infantis cells are incorporated into its proteome. This indicates that NAG, an amino sugar residue of human milk oligosaccharides (HMO) and other biopolymers, is used as a nitrogen source. Transcriptomics while subsisting on NAG nitrogen are consistent with the proteomics results. This further indicates that B. infantis utilizes NAG nitrogen in and shunts it towards a fundamental cellular processes.
2023-05-18 | PXD035809 | Pride
Project description:Bifidobacterium longum subsp. infantis (B. infantis) resides in the human infant gut and helps with the utilization of human milk-derived nutrient components. While its utilization of various carbohydrate sources has been studied extensively, mechanisms behind utilization of nitrogen components from human milk remain largely unknown. In this study, we present B. infantis growth profiles on the N-containing human milk oligosaccharides (HMO) as nitrogen sources, namely, lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT). Dietary 2-Oxoglutarate (2-OG) in known in mice model for its protective effects against intestinal inflammation and colitis development. In this study, we have shown that B. infantis had increased 2-OG concentration when utilizes LNT or LNnT as a primary nitrogen source. As LNT and LNnT are the isomers of HMO core structures, N-acetyl glucosamine (NAG), the N-containing monosaccharide, was regarded as the nitrogen provider of the HMO core structures. Differentially expressed gene patterns in B. infantis were analyzed under the less efficient nitrogen conditions (HMOs and NAG) relative to the complex nitrogen controls. Proteomics analysis of B. infantis using 15N-labeled NAG revealed that NAG nitrogen was incorporated into B. infantis metabolism. Transcriptomics results of B. infantis in LNT, LNnT and NAG nitrogen were consistent with the proteomics results. This further indicated that B. infantis metabolism was affected by NAG nitrogen in nitrogen assimilation, HMO catabolism, NAD cofactor biosynthesis and regeneration, and peptidoglycan biosynthesis pathways. In summary, B. infantis can use NAG-containing HMO as a nitrogen source and incorporate NAG nitrogen into metabolism pathways.
2023-09-14 | GSE209665 | GEO