scholarly journals Sex Chromosomes and Sex Phenotype Contribute to Biased DNA Methylation in Mouse Liver

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1436
Author(s):  
Qinwei Kim-Wee Zhuang ◽  
Jose Hector Galvez ◽  
Qian Xiao ◽  
Najla AlOgayil ◽  
Jeffrey Hyacinthe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Wide Distribution ◽  
Sex Bias ◽  
Partial Conservation ◽  
Genome Bisulfite Sequencing ◽  
Sex Biases

Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our understanding of the mechanisms that contribute to sex biases in DNA methylation and gene expression, we conducted whole genome bisulfite sequencing (WGBS) as well as RNA-seq on liver samples from mice with different combinations of sex phenotype and sex-chromosome complement. We compared groups of animals with different sex phenotypes, but the same genetic sexes, and vice versa, same sex phenotypes, but different sex-chromosome complements. We also compared sex-biased DNA methylation in mouse and human livers. Our data show that sex phenotype, X-chromosome dosage, and the presence of Y chromosome shape the differences in DNA methylation between males and females. We also demonstrate that sex bias in autosomal methylation is associated with sex bias in gene expression, whereas X-chromosome dosage-dependent methylation differences are not, as expected for a dosage-compensation mechanism. Furthermore, we find partial conservation between the repertoires of mouse and human genes that are associated with sex-biased methylation, an indication that gene function is likely to be an important factor in this phenomenon.

scholarly journals Differential regulation of mouse hippocampal gene expression sex differences by chromosomal content and gonadal sex

2021 ◽  
Author(s):  
Sarah R Ocanas ◽  
Victor A Ansere ◽  
Kyla B Tooley ◽  
Niran Hadad ◽  
Ana J Chucair-Elliott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sex Differences ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Experimental Models ◽  
Ctcf Binding ◽  
Autosomal Gene ◽  
Sex Effects

Sex differences in the brain as they relate to health and disease are often overlooked in experimental models. Many neurological disorders, like Alzheimer's disease (AD), multiple sclerosis (MS), and autism, differ in prevalence between males and females. Sex differences originate either from differential gene expression on sex chromosomes or from hormonal differences, either directly or indirectly. To disentangle the relative contributions of genetic sex (XX v. XY) and gonadal sex (ovaries v. testes) to the regulation of hippocampal sex effects, we use the "sex-reversal" Four Core Genotype (FCG) mouse model which uncouples sex chromosome complement from gonadal sex. Transcriptomic and epigenomic analyses of hippocampal RNA and DNA from ~12 month old FCG mice, reveals differential regulatory effects of sex chromosome content and gonadal sex on X- versus autosome-encoded gene expression and DNA modification patterns. Gene expression and DNA methylation patterns on the X chromosome were driven primarily by sex chromosome content, not gonadal sex. The majority of DNA methylation changes involved hypermethylation in the XX genotypes (as compared to XY) in the CpG context, with the largest differences in CpG islands, promoters, and CTCF binding sites. Autosomal gene expression and DNA modifications demonstrated regulation by sex chromosome complement and gonadal sex. These data demonstrate the importance of sex chromosomes themselves, independent of hormonal status, in regulating hippocampal sex effects. Future studies will need to further interrogate specific CNS cell types, identify the mechanisms by which sex chromosome regulate autosomes, and differentiate organizational from activational hormonal effects.

scholarly journals DNA Methylation Patterns in the Social Spider, Stegodyphus dumicola

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 137 ◽  
Author(s):  
Shenglin Liu ◽  
Anne Aagaard ◽  
Jesper Bechsgaard ◽  
Trine Bilde
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sequence Data ◽  
Social Spider ◽  
The Social ◽  
Genome Bisulfite Sequencing ◽  
Differential Gene ◽  
Methylation Patterns ◽  
Comparative Phylogenetic Analysis

Variation in DNA methylation patterns among genes, individuals, and populations appears to be highly variable among taxa, but our understanding of the functional significance of this variation is still incomplete. We here present the first whole genome bisulfite sequencing of a chelicerate species, the social spider Stegodyphus dumicola. We show that DNA methylation occurs mainly in CpG context and is concentrated in genes. This is a pattern also documented in other invertebrates. We present RNA sequence data to investigate the role of DNA methylation in gene regulation and show that, within individuals, methylated genes are more expressed than genes that are not methylated and that methylated genes are more stably expressed across individuals than unmethylated genes. Although no causal association is shown, this lends support for the implication of DNA CpG methylation in regulating gene expression in invertebrates. Differential DNA methylation between populations showed a small but significant correlation with differential gene expression. This is consistent with a possible role of DNA methylation in local adaptation. Based on indirect inference of the presence and pattern of DNA methylation in chelicerate species whose genomes have been sequenced, we performed a comparative phylogenetic analysis. We found strong evidence for exon DNA methylation in the horseshoe crab Limulus polyphemus and in all spider and scorpion species, while most Parasitiformes and Acariformes species seem to have lost DNA methylation.

scholarly journals Adenine DNA methylation, 3D genome organization, and gene expression in the parasiteTrichomonas vaginalis

2020 ◽  
Vol 117 (23) ◽  
pp. 13033-13043
Author(s):  
Ayelen Lizarraga ◽  
Zach Klapholz O’Brown ◽  
Konstantinos Boulias ◽  
Lara Roach ◽  
Eric Lieberman Greer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Trichomonas Vaginalis ◽  
Three Dimensional ◽  
Wide Distribution ◽  
Spatial Proximity ◽  
Regulation Of Transcription ◽  
3D Genome ◽  
Intergenic Regions ◽  
Close Spatial Proximity

Trichomonas vaginalisis a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine (5mC), is the main DNA methylation mark inT. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA inT. vaginalisis associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

scholarly journals X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils

2010 ◽  
Vol 107 (8) ◽  
pp. 3704-3709 ◽  
Author(s):  
Yukio Yasukochi ◽  
Osamu Maruyama ◽  
Milind C. Mahajan ◽  
Carolyn Padden ◽  
Ghia M. Euskirchen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
X Chromosome ◽  
Genomic Dna ◽  
Male And Female

Changes in DNA methylation during mouse embryonic development in relation to X-chromosome activity and imprinting

1990 ◽  
Vol 326 (1235) ◽  
pp. 299-312 ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
X Chromosome ◽  
De Novo ◽  
Germ Line ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromatin Configuration ◽  
Methylation Patterns

Changing DNA methylation patterns during embryonic development are discussed in relation to differential gene expression, changes in X-chromosome activity and genomic imprinting. Sperm DNA is more methylated than oocyte DNA, both overall and for specific sequences. The methylation difference between the gametes could be one of the mechanisms (along with chromatin structure) regulating initial differences in expression of parental alleles in early development. There is a loss of methylation during development from the morula to the blastocyst and a marked decrease in methylase activity. De novo methylation becomes apparent around the time of implantation and occurs to a lesser extent in extra-embryonic tissue DNA. In embryonic DNA, de novo methylation begins at the time of random X-chromosome inactivation but it continues to occur after X-chromosome inactivation and may be a mechanism that irreversibly fixes specific patterns of gene expression and X-chromosome inactivity in the female. The germ line is probably delineated before extensive de novo methylation and hence escapes this process. The marked undermethylation of the germ line DNA may be a prerequisite for X-chromosome reactivation. The process underlying reactivation and removal of parent-specific patterns of gene expression may be changes in chromatin configuration associated with meiosis and a general reprogramming of the germ line to developmental totipotency.

scholarly journals Sex differences in gene expression and proliferation are dependent on the epigenetic modifier HP1γ

2019 ◽  
Author(s):  
Pui-Pik Law ◽  
Ping-Kei Chan ◽  
Kirsten McEwen ◽  
Huihan Zhi ◽  
Bing Liang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Autosomal Gene ◽  
Sexually Dimorphic ◽  
Heterochromatin Protein 1 ◽  
Epigenetic Modifier ◽  
Early Embryos ◽  
Males And Females

SummarySex differences in growth rate in very early embryos have been recognized in a variety of mammals and attributed to sex-chromosome complement effects as they occur before overt sexual differentiation. We previously found that sex-chromosome complement, rather than sex hormones regulates heterochromatin-mediated silencing of a transgene and autosomal gene expression in mice. Here, sex dimorphism in proliferation was investigated. We confirm that male embryonic fibroblasts proliferate faster than female fibroblasts and show that this proliferation advantage is completely dependent upon heterochromatin protein 1 gamma (HP1γ). To determine whether this sex-regulatory effect of HP1γ was a more general phenomenon, we performed RNA sequencing on MEFs derived from males and females, with or without HP1γ. Strikingly, HP1γ was found to be crucial for regulating nearly all sexually dimorphic autosomal gene expression because deletion of the HP1γ gene in males abolished sex differences in autosomal gene expression. The identification of a key epigenetic modifier as central in defining gene expression differences between males and females has important implications for understanding physiological sex differences and sex bias in disease.

scholarly journals Identification of sex chromosomes using genomic and cytogenetic methods in a range-expanding spider, Argiope bruennichi (Araneae: Araneidae)

2021 ◽  
Author(s):  
Monica M Sheffer ◽  
Mathilde M Cordellier ◽  
Martin Forman ◽  
Malte Grewoldt ◽  
Katharina Hoffmann ◽  
...  
Keyword(s):  
X Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Gc Content ◽  
Sexually Dimorphic ◽  
Behavioral Experiments ◽  
X Chromosomes ◽  
Male Karyotype ◽  
And Behavior

Differences between sexes in growth, ecology and behavior strongly shape species biology. In some animal groups, such as spiders, it is difficult or impossible to identify the sex of juveniles. This information would be useful for field surveys, behavioral experiments, and ecological studies on e.g. sex ratios and dispersal. In species with sex chromosomes, sex can be determined based on the specific sex chromosome complement. Additionally, information on the sequence of sex chromosomes provides the basis for studying sex chromosome evolution. We combined cytogenetic and genomic data to identify the sex chromosomes in the sexually dimorphic spider Argiope bruennichi, and designed RT-qPCR sex markers. We found that genome size and GC content of this spider falls into the range reported for the majority of araneids. The male karyotype is formed by 24 acrocentric chromosomes with an X1X20 sex chromosome system, with little similarity between X chromosomes, suggesting origin of these chromosomes by X chromosome fission or early duplication of an X chromosome and subsequent independent differentiation of the copies. Our data suggest similarly sized X chromosomes in A. bruennichi. They are smaller chromosomes of the complement. Our findings open the door to new directions in spider evolutionary and ecological research.

scholarly journals DNA Methylation and Transcriptomic Features are Preserved Throughout Disease Recurrence and Chemoresistance in High Grade Serous Ovarian Cancers

2022 ◽  
Author(s):  
Nicole Gull ◽  
Michell Jones ◽  
Pei-Chen Peng ◽  
Simon Coetzee ◽  
Tiago Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Disease Recurrence ◽  
High Grade ◽  
Chemotherapy Treatment ◽  
Recurrent Tumors ◽  
Genome Wide ◽  
Genome Bisulfite Sequencing

Abstract Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations. Results Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P=0.006) in these BRCA1/2 carriers. Conclusions These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.

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