scholarly journals Parent of origin gene expression in a founder population identifies two new imprinted genes at known imprinted regions

2018 ◽  
Author(s):  
Sahar V. Mozaffari ◽  
Michelle M. Stein ◽  
Kevin M. Magnaye ◽  
Dan L. Nicolae ◽  
Carole Ober
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Expression Data ◽  
Imprinted Genes ◽  
Genotype Data ◽  
Expression Data ◽  
Rna Seq ◽  
Specific Expression ◽  
Allele Specific ◽  
Parent Of Origin

AbstractGenomic imprinting is the phenomena that leads to silencing of one copy of a gene inherited from a specific parent. Mutations in imprinted regions have been involved in diseases showing parent of origin effects. Identifying genes with evidence of parent of origin expression patterns in family studies allows the detection of more subtle imprinting. Here, we use allele specific expression in lymphoblastoid cell lines from 306 Hutterites related in a single pedigree to provide formal evidence for parent of origin effects. We take advantage of phased genotype data to assign parent of origin to RNA-seq reads in individuals with gene expression data. Our approach identified known imprinted genes, two putative novel imprinted genes, and 14 genes with asymmetrical parent of origin gene expression. We used gene expression in peripheral blood leukocytes (PBL) to validate our findings, and then confirmed imprinting control regions (ICRs) using DNA methylation levels in the PBLs.Author SummaryLarge scale gene expression studies have identified known and novel imprinted genes through allele specific expression without knowing the parental origins of each allele. Here, we take advantage of phased genotype data to assign parent of origin to RNA-seq reads in 306 individuals with gene expression data. We identified known imprinted genes as well as two novel imprinted genes in lymphoblastoid cell line gene expression. We used gene expression in PBLs to validate our findings, and DNA methylation levels in PBLs to confirm previously characterized imprinting control regions that could regulate these imprinted genes.

scholarly journals Bumblebee worker castes show differences in allele-specific DNA methylation and allele-specific expression

2020 ◽  
Author(s):  
H. Marshall ◽  
A.R.C. Jones ◽  
Z.N. Lonsdale ◽  
E.B. Mallon
Keyword(s):  
Dna Methylation ◽  
Bombus Terrestris ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Genome Wide ◽  
Expression Bias ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Worker Castes

AbstractAllele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Genomic imprinting is an extreme example of this, where some genes exhibit allele-specific expression in a parent-of-origin manner. Recent work has identified potentially imprinted genes in species of Hymenoptera. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with imprinted genes. DNA methylation systems have been described in species of Hymenoptera, providing a candidate imprinting mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive castes and the proportion of allele-specific expression bias generally varies between colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both castes. There is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that DNA methylation does not directly drive genome-wide allele-specific expression in this species. Only a small number of the genes identified may be ‘imprinted’ and it may be these genes which are associated with allele-specific DNA methylation. Future work utilising reciprocal crosses to identify parent-of-origin DNA methylation will further clarify the role of DNA methylation in parent-of-origin allele-specific expression.

scholarly journals Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting

2021 ◽  
Vol 118 (29) ◽  
pp. e2104445118
Author(s):  
Jessica A. Rodrigues ◽  
Ping-Hung Hsieh ◽  
Deling Ruan ◽  
Toshiro Nishimura ◽  
Manoj K. Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genomic Imprinting ◽  
Small Rnas ◽  
Imprinted Genes ◽  
Dna Hypomethylation ◽  
Transcription Start ◽  
Specific Expression ◽  
Parent Of Origin

Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.

scholarly journals H3K9 methyltransferase EHMT2/G9a controls ERVK-driven noncanonical imprinted genes

Epigenomics ◽  
2021 ◽  
Author(s):  
Tie-Bo Zeng ◽  
Nicholas Pierce ◽  
Ji Liao ◽  
Piroska E Szabó
Keyword(s):  
Dna Methylation ◽  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Paternal Allele ◽  
Imprinted Genes ◽  
Rna Seq ◽  
Maternal Allele ◽  
Specific Expression ◽  
Allele Specific ◽  
Ectoplacental Cone

Aim: Paternal allele-specific expression of noncanonical imprinted genes in the extraembryonic lineages depends on an H3K27me3-based imprint in the oocyte, which is not a lasting mark. We hypothesized that EHMT2, the main euchromatic H3K9 dimethyltransferase, also has a role in controlling noncanonical imprinting. Methods: We carried out allele-specific total RNA-seq analysis in the ectoplacental cone of somite-matched 8.5 days post coitum embryos using reciprocal mouse crosses. Results: We found that the maternal allele of noncanonical imprinted genes was derepressed from its ERVK promoter in the Ehmt2-/- ectoplacental cone. In Ehmt2-/- embryos, loss of DNA methylation accompanied biallelic derepression of the ERVK promoters. Canonical imprinting and imprinted X chromosome inactivation were generally undisturbed. Conclusion: EHMT2 is essential for repressing the maternal allele in noncanonical imprinting.

scholarly journals Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprinting

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Daniela Pignatta ◽  
Robert M Erdmann ◽  
Elias Scheer ◽  
Colette L Picard ◽  
George W Bell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Seed Development ◽  
Intraspecific Variation ◽  
Small Rnas ◽  
Expression Patterns ◽  
Imprinted Genes ◽  
Standing Variation ◽  
Allele Specific ◽  
Parent Of Origin

Imprinted gene expression occurs during seed development in plants and is associated with differential DNA methylation of parental alleles, particularly at proximal transposable elements (TEs). Imprinting variability could contribute to observed parent-of-origin effects on seed development. We investigated intraspecific variation in imprinting, coupled with analysis of DNA methylation and small RNAs, among three Arabidopsis strains with diverse seed phenotypes. The majority of imprinted genes were parentally biased in the same manner among all strains. However, we identified several examples of allele-specific imprinting correlated with intraspecific epigenetic variation at a TE. We successfully predicted imprinting in additional strains based on methylation variability. We conclude that there is standing variation in imprinting even in recently diverged genotypes due to intraspecific epiallelic variation. Our data demonstrate that epiallelic variation and genomic imprinting intersect to produce novel gene expression patterns in seeds.

scholarly journals H3K9 methyltransferase EHMT2/G9a controls ERVK-driven non-canonical imprinted genes

2021 ◽  
Author(s):  
Tie-Bo Zeng ◽  
Nicholas Pierce ◽  
Piroska Szabo
Keyword(s):  
Dna Methylation ◽  
Paternal Allele ◽  
Imprinted Genes ◽  
Rna Seq ◽  
Maternal Allele ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Methylation Difference ◽  
Allele Specific ◽  
Ectoplacental Cone

Unlike regular imprinted genes, non-canonical imprinted genes are known to not depend on gamete-specific DNA methylation difference. Instead, the paternal allele-specific expression of these genes in the extra-embryonic lineages depends on an H3K27me3-based imprint in the oocyte, but this marking is not maintained beyond pre-implantation development. The maintenance of non-canonical imprinting corresponds to maternal allele-specific DNA methylation and paternal allele-specific H3K4me3 at their somatic DMRs, which occur at ERVK repeats. We hypothesized that EHMT2, the main euchromatic H3K9 methyltransferase, also has a role in this process. Using reciprocal mouse crosses and allele-specific RNA-seq analysis, we found that the maternal allele of each known non-canonical imprinted gene was derepressed from its ERVK promoter in the Ehmt2−/− ectoplacental cone of somite-matched 8.5 dpc embryos. In the Ehmt2−/− embryos, loss of DNA methylation accompanied the derepression of both parental alleles of those ERVK promoters. Our study identifies EHMT2 as an essential player that maintains the repressed chromosomal state in non-canonical imprinting.

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

Identification of functionally methylated regions based on discriminant analysis through integrating methylation and gene expression data

2015 ◽  
Vol 11 (7) ◽  
pp. 1786-1793 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Junying Zhang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Discriminant Analysis ◽  
Gene Expression Data ◽  
Cellular Differentiation ◽  
Expression Data

DNA methylation is essential not only in cellular differentiation but also in diseases.

scholarly journals Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types

2017 ◽  
Author(s):  
Hilary K. Finucane ◽  
Yakir A. Reshef ◽  
Verneri Anttila ◽  
Kamil Slowikowski ◽  
Alexander Gusev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Complex Disease ◽  
Genome Wide Association Study ◽  
Ex Vivo ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Biliary Cirrhosis ◽  
Expression Data ◽  
Specific Expression

ABSTRACTGenetics can provide a systematic approach to discovering the tissues and cell types relevant for a complex disease or trait. Identifying these tissues and cell types is critical for following up on non-coding allelic function, developing ex-vivo models, and identifying therapeutic targets. Here, we analyze gene expression data from several sources, including the GTEx and PsychENCODE consortia, together with genome-wide association study (GWAS) summary statistics for 48 diseases and traits with an average sample size of 169,331, to identify disease-relevant tissues and cell types. We develop and apply an approach that uses stratified LD score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We detect tissue-specific enrichments at FDR < 5% for 34 diseases and traits across a broad range of tissues that recapitulate known biology. In our analysis of traits with observed central nervous system enrichment, we detect an enrichment of neurons over other brain cell types for several brain-related traits, enrichment of inhibitory over excitatory neurons for bipolar disorder but excitatory over inhibitory neurons for schizophrenia and body mass index, and enrichments in the cortex for schizophrenia and in the striatum for migraine. In our analysis of traits with observed immunological enrichment, we identify enrichments of T cells for asthma and eczema, B cells for primary biliary cirrhosis, and myeloid cells for Alzheimer's disease, which we validated with independent chromatin data. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signal.

scholarly journals IRIS-EDA: An integrated RNA-Seq interpretation system for gene expression data analysis

2019 ◽  
Vol 15 (2) ◽  
pp. e1006792 ◽  
Author(s):  
Brandon Monier ◽  
Adam McDermaid ◽  
Cankun Wang ◽  
Jing Zhao ◽  
Allison Miller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Data Analysis ◽  
Gene Expression Data ◽  
Expression Data ◽  
Rna Seq ◽  
Gene Expression Data Analysis ◽  
Interpretation System
Sign in / Sign up

Export Citation Format

Share Document