Homo sapiens strain:lymphoblastoid cells
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PROVIDER: PRJNA229064 | ENA |
REPOSITORIES: ENA
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Project description:In this experiment, we asked how the allelic distribution of the active and repressive chromatin marks in clonal cell lines relates to the transcriptional allelic bias. A multiplexed padlock probe approach (Zhang et al., 2009) enabled us to assess allelic bias in heterozygous exonic SNPs in two clones with GM12878 genotype, and four clones from GM13130 cells. We used this approach to assess allelic bias in H3K27me3 and H3K36me3 ChIP samples simultaneously with cDNA from the same cells, as well as ChIP input and genomic DNA controls. In order to pool data from two individuals, one of which (GM13130) lacked complete genotypes for parents, we assessed SNP bias as reference and alternative alleles (rather than maternal or paternal bias). SNPs in cDNA were assigned to one of three bins: reference allele bias; no bias; and alternative allele bias. For these groups, allelic bias in H3K27me3 (Fig.4B) and H3K36me3 (Fig.4C) was determined. In unbiased loci, both H3K27me3 and H3K36me3 were equally represented. In contrast, preferential expression of an allele was associated with elevated levels of H3K36me3 and decreased levels of H3K27me3 on that allele. Both effects were highly significant (p<2x10e-9). Genes predicted to have MAE were about four-fold over-represented among genes where SNPs showed significant bias (Fig.4D). SNPs with skewed H3K27me3 and H3K36me3 distribution were highly enriched in the genes predicted as MAE (p<10e-6 and p=0.01, respectively; two-tailed Fisher's exact test). This suggests that the asymmetric distribution of the histone modifications is to a large extent due to the genes that have the chromatin signature of monoallelic expression. Samples analyzed were A. polyclonal cell line GM12878 , and clones derived from it: DF1 and DF2, B. Polyclonal GM13130 (H0) and clones derived from it: H7, H14 and H16. gDNA, cDNA, ChIP material and input were used.
2014-02-07 | E-GEOD-53628 | biostudies-arrayexpress
Project description:In this experiment, we asked how the allelic distribution of the active and repressive chromatin marks in clonal cell lines relates to the transcriptional allelic bias. A multiplexed padlock probe approach (Zhang et al., 2009) enabled us to assess allelic bias in heterozygous exonic SNPs in two clones with GM12878 genotype, and four clones from GM13130 cells. We used this approach to assess allelic bias in H3K27me3 and H3K36me3 ChIP samples simultaneously with cDNA from the same cells, as well as ChIP input and genomic DNA controls. In order to pool data from two individuals, one of which (GM13130) lacked complete genotypes for parents, we assessed SNP bias as reference and alternative alleles (rather than maternal or paternal bias). SNPs in cDNA were assigned to one of three bins: reference allele bias; no bias; and alternative allele bias. For these groups, allelic bias in H3K27me3 (Fig.4B) and H3K36me3 (Fig.4C) was determined. In unbiased loci, both H3K27me3 and H3K36me3 were equally represented. In contrast, preferential expression of an allele was associated with elevated levels of H3K36me3 and decreased levels of H3K27me3 on that allele. Both effects were highly significant (p<2x10e-9). Genes predicted to have MAE were about four-fold over-represented among genes where SNPs showed significant bias (Fig.4D). SNPs with skewed H3K27me3 and H3K36me3 distribution were highly enriched in the genes predicted as MAE (p<10e-6 and p=0.01, respectively; two-tailed Fisher's exact test). This suggests that the asymmetric distribution of the histone modifications is to a large extent due to the genes that have the chromatin signature of monoallelic expression.
2014-02-07 | GSE53628 | GEO
Project description:Cis-regulatory variants are predicted to mediate the majority of the common genetic risk associated to complex disease, yet the specific causal variants have thus far been poorly characterized. Allele-specific (AS) assessment of chromatin modifications has the potential to elucidate specific cis-regulatory mechanisms. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depth not commonly applied in next-generation sequencing based approaches. In this study, we addressed this by directly assessing AS chromatin states through parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. Allele-specificity of chromatin was assessed in 14 lymphoblast and 6 fibroblast cell lines by assaying PolII & histone ChIP samples (H3K4me1, H3K4me3, H3K27ac, H3K27me3, H3K36me3) in parallel with gDNA and cDNA on high-density Illumina genotyping arrays.
2013-10-18 | E-GEOD-51272 | biostudies-arrayexpress
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:Analysis of differential expression using the 3’ expression module revealed 34% probe sets showed evidence for a sex bias and alternative exon sex bias was identified for 164 genes. Intriguingly, allelic imbalance was detected for 37% of 6,579 probe sets examined which contained heterozygous SNP loci.
2011-09-13 | GSE31750 | GEO
Project description:Analysis of differential expression using the 3’ expression module revealed 34% probe sets showed evidence for a sex bias and alternative exon sex bias was identified for 164 genes. Intriguingly, allelic imbalance was detected for 37% of 6,579 probe sets examined which contained heterozygous SNP loci. Two different isogenic strains of D. simulans, st e and C167.4 and their male and female progeny were used as the basis for the verification study. Three replicates of RNA from female and male progeny of the cross st e x C167.4 made for a total of six RNA samples. In addition, DNA was used as a control for estimating allele imbalance. Three replicates of DNA target were prepared for female st e, femaleC167.4 and the female F1 progeny of the cross st e x C167.4, for a total of 9 gDNA samples.
2011-09-12 | E-GEOD-31750 | biostudies-arrayexpress
Project description:We did ChIP-seq with anti- H3K4me3, H3K4me1, H3K4me2, H3K27me3, H3K27ac, and H3K36me3 antibodies in both C2C12 myoblasts and myotubes
2013-08-24 | GSE33227 | GEO
Project description:Mechanism, inheritance patterns and biological significance remain unclear. Here, we generated genome-wide integrated maps of H3K27me3 modification and transcriptome for Col, C24 and their F1 hybrid, and their clf mutants. We found that H3K27me3 modification profiles were divergent between Col and C24, and were inherited mainly additively in hybrid. By comparing H3K27me3 modification ratio between parents to allelic H3K27me3 modification ratio in hybrid, we identified cis- and trans-regulatory divergence for H3K27me3 modification variation between Col and C24, and found that cis-regulatory divergence was the predominant contributor to H3K27me3 variation. The majority of genes with both cis- and trans-regulatory divergence displayed "cis-trans" interaction, whereas "cis+trans" interaction resulted in higher magnitude of H3K27me3 variation. H3K27me3 modification variation was negatively correlated with gene expression variation between Col and C24, both of which might rise from the same cis-regulatory divergence. Moreover, cis-regulatory divergence could lead to the concurrent allelic H3K27me3 modification bias and allelic gene expression bias for auxin metabolic genes and stimulus responsive genes in Col×C24 hybrid. Natural variation of H3K27me3 modification and gene expression were changed upon CLF mutation, and heterosis, especially best-parent hetereosis, was largely compromised in clf hybrid. Together, our study provided a comprehensive analysis of regulatory divergence for natural variation of histone modification and its association with differential gene expression between Arabidopsis accessions and growth vigor in hybrid.
2016-11-01 | GSE62615 | GEO
Project description:Cis-regulatory variants are predicted to mediate the majority of the common genetic risk associated to complex disease, yet the specific causal variants have thus far been poorly characterized. Allele-specific (AS) assessment of chromatin modifications has the potential to elucidate specific cis-regulatory mechanisms. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depth not commonly applied in next-generation sequencing based approaches. In this study, we addressed this by directly assessing AS chromatin states through parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines.
2013-10-18 | GSE51272 | GEO