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 AFF3-DNA methylation interplay in maintaining the mono-allelic expression pattern of XIST in terminally differentiated cells

2018 ◽  
Vol 11 (9) ◽  
pp. 761-769 ◽  
Author(s):  
Yue Zhang ◽  
Chao Wang ◽  
Xiaoxu Liu ◽  
Qian Yang ◽  
Hongliang Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Pattern ◽  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Allelic Expression ◽  
Elongation Complex ◽  
Regulatory Processes ◽  
Differentiated Cells

Abstract X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression. In female mammals, mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript (XIST) is essential for initiation of X chromosome inactivation upon differentiation. We have previously demonstrated that the central factor of super elongation complex-like 3 (SEC-L3), AFF3, is enriched at gamete differentially methylated regions (DMRs) of the imprinted loci and regulates the imprinted gene expression. Here, we found that AFF3 can also bind to the DMR downstream of the XIST promoter. Knockdown of AFF3 leads to de-repression of the inactive allele of XIST in terminally differentiated cells. In addition, the binding of AFF3 to the XIST DMR relies on DNA methylation and also regulates DNA methylation level at DMR region. However, the KAP1-H3K9 methylation machineries, which regulate the imprinted loci, might not play major roles in maintaining the mono-allelic expression pattern of XIST in these cells. Thus, our results suggest that the differential mechanisms involved in the XIST DMR and gDMR regulation, which both require AFF3 and DNA methylation.

scholarly journals Molecular signatures of X chromosome inactivation and associations with clinical outcomes in epithelial ovarian cancer

2018 ◽  
Vol 28 (8) ◽  
pp. 1331-1342 ◽  
Author(s):  
Stacey J Winham ◽  
Nicholas B Larson ◽  
Sebastian M Armasu ◽  
Zachary C Fogarty ◽  
Melissa C Larson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Dna Methylation ◽  
X Chromosome ◽  
Strong Association ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Specific Expression ◽  
Cluster Membership ◽  
Promoter Dna

AbstractX chromosome inactivation (XCI) is a key epigenetic gene expression regulatory process, which may play a role in women’s cancer. In particular tissues, some genes are known to escape XCI, yet patterns of XCI in ovarian cancer (OC) and their clinical associations are largely unknown. To examine XCI in OC, we integrated germline genotype with tumor copy number, gene expression and DNA methylation information from 99 OC patients. Approximately 10% of genes showed different XCI status (either escaping or being subject to XCI) compared with the studies of other tissues. Many of these genes are known oncogenes or tumor suppressors (e.g. DDX3X, TRAPPC2 and TCEANC). We also observed strong association between cis promoter DNA methylation and allele-specific expression imbalance (P = 2.0 × 10−10). Cluster analyses of the integrated data identified two molecular subgroups of OC patients representing those with regulated (N = 47) and dysregulated (N = 52) XCI. This XCI cluster membership was associated with expression of X inactive specific transcript (P = 0.002), a known driver of XCI, as well as age, grade, stage, tumor histology and extent of rl disease following surgical debulking. Patients with dysregulated XCI (N = 52) had shorter time to recurrence (HR = 2.34, P = 0.001) and overall survival time (HR = 1.87, P = 0.02) than those with regulated XCI, although results were attenuated after covariate adjustment. Similar findings were observed when restricted to high-grade serous tumors. We found evidence of a unique OC XCI profile, suggesting that XCI may play an important role in OC biology. Additional studies to examine somatic changes with paired tumor-normal tissue are needed.

Random X-chromosome inactivation in female primordial germ cells in the mouse

Development ◽  
1981 ◽  
Vol 64 (1) ◽  
pp. 251-258
Author(s):  
Andy McMahon ◽  
Mandy Fosten ◽  
Marilyn Monk
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Phosphoglycerate Kinase ◽  
X Chromosome Inactivation ◽  
Yolk Sac ◽  
Chromosome Inactivation ◽  
X Chromosomes

The pattern of expression of the two X chromosomes was investigated in pre-meiotic germ cells from 12½-day-old female embryos heterozygous for the variant electrophoretic forms of the X-linked enzyme phosphoglycerate kinase (PGK-1). If such germ cells carry the preferentially active Searle's translocated X chromosome (Lyon, Searle, Ford & Ohno, 1964), then only the Pgk-1 allele on this chromosome is expressed. This confirms Johnston's evidence (1979,1981) that Pgk-1 expression reflects a single active X chromosome at this time. Extracts of 12½-day germ cells from heterozygous females carrying two normal X chromosomes show both the A and the B forms of PGK; since only one X chromosome in each cell is active, different alleles must be expressed in different cells, suggesting that X-chromosome inactivation is normally random in the germ line. This result makes it unlikely that germ cells are derived from the yolk-sac endoderm where the paternally derived X chromosome is preferentially inactivated. In their pattern of X-chromosome inactivation, germ cells evidently resemble other tissues derived from the epiblast.

scholarly journals Nurse cell-derived small RNAs define paternal epigenetic inheritance in Arabidopsis

2021 ◽  
Author(s):  
Jincheng Long ◽  
James Walker ◽  
Wenjing She ◽  
Billy Aldridge ◽  
Hongbo Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
Nurse Cell ◽  
De Novo ◽  
Epigenetic Inheritance ◽  
Genome Integrity ◽  
Nurse Cells ◽  
Male Germline ◽  
Methylation Patterns

AbstractThe plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and facilitates meiosis. Why reprogramming is limited to the germline and how specific genes are chosen is unknown. Here, we demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by germline-specific siRNAs transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) via activity of the tapetum-specific chromatin remodeler CLASSY3. Remarkably, tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Finally, we demonstrate that these nurse cell-derived siRNAs (niRNAs) silence germline transposons, thereby safeguarding genome integrity. Our results reveal that tapetal niRNAs are sufficient to reconstitute germline methylation patterns and drive extensive, functional methylation reprogramming analogous to piRNA-mediated reprogramming in animal germlines.

scholarly journals Landscape of X chromosome inactivation across human tissues

Nature ◽  
2017 ◽  
Vol 550 (7675) ◽  
pp. 244-248 ◽  
Author(s):  
Taru Tukiainen ◽  
◽  
Alexandra-Chloé Villani ◽  
Angela Yen ◽  
Manuel A. Rivas ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Mammalian Cells ◽  
Phenotypic Diversity ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Phenotypic Traits ◽  
Human Tissues ◽  
X Chromosomes ◽  
Chromosomal Genes

Abstract X chromosome inactivation (XCI) silences transcription from one of the two X chromosomes in female mammalian cells to balance expression dosage between XX females and XY males. XCI is, however, incomplete in humans: up to one-third of X-chromosomal genes are expressed from both the active and inactive X chromosomes (Xa and Xi, respectively) in female cells, with the degree of ‘escape’ from inactivation varying between genes and individuals1,2. The extent to which XCI is shared between cells and tissues remains poorly characterized3,4, as does the degree to which incomplete XCI manifests as detectable sex differences in gene expression5 and phenotypic traits6. Here we describe a systematic survey of XCI, integrating over 5,500 transcriptomes from 449 individuals spanning 29 tissues from GTEx (v6p release) and 940 single-cell transcriptomes, combined with genomic sequence data. We show that XCI at 683 X-chromosomal genes is generally uniform across human tissues, but identify examples of heterogeneity between tissues, individuals and cells. We show that incomplete XCI affects at least 23% of X-chromosomal genes, identify seven genes that escape XCI with support from multiple lines of evidence and demonstrate that escape from XCI results in sex biases in gene expression, establishing incomplete XCI as a mechanism that is likely to introduce phenotypic diversity6,7. Overall, this updated catalogue of XCI across human tissues helps to increase our understanding of the extent and impact of the incompleteness in the maintenance of XCI.

139 SEX-SPECIFIC GENE EXPRESSION IN PORCINE PRE-IMPLANTATION EMBRYOS

2016 ◽  
Vol 28 (2) ◽  
pp. 199
Author(s):  
D. Kradolfer ◽  
J. Knubben ◽  
V. Flöter ◽  
J. Bick ◽  
S. Bauersachs ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Current Knowledge ◽  
Critical Time ◽  
Blastocyst Stage ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Specific Gene ◽  
Embryo Survival ◽  
Specific Gene Expression

X-Chromosome inactivation in female mammals starts during early blastocyst stage with expression of the X-inactive specific transcript (XIST), which coats and silences the inactive X chromosome. However, this compensation is not complete in blastocysts, as a large number of X-linked transcripts are more highly expressed in female embryos than in males. Furthermore, the process of X chromosome inactivation is altered in IVF and cloned porcine embryos, possibly explaining problems of embryo survival with these techniques. The aim of this study was to gain more insights into the transcriptional dynamics of the porcine pre-implantation embryo, with a particular focus on sex-specific differences. RNA sequencing (RNA-Seq) was performed for individual blastocysts at 8, 10, and 12 days after ovulation, and the temporal development of sex-specific transcripts was analysed. German Landrace sows were cycle synchronized and inseminated with sperm of the same Pietrain boar. On Days 8, 10, and 12 post-insemination, sows were slaughtered and embryos were removed from the uterus using 10 mL of PBS (pH 7.4) per horn. Single embryos were shock frozen in liquid nitrogen and stored at –80°C until the extraction of RNA and DNA (AllPrep DNA/RNA Micro Kit, Qiagen, Valencia, CA, USA). Using the isolated DNA, the sex of the embryos was determined and 5 female and male embryos, respectively, were analysed per stage. Illumina TruSeq Stranded mRNA libraries (Illumina Inc., San Diego, CA, USA) were sequenced on a HiSEqn 2500 (Illumina Inc.), and 15 to 25 million 100-bp single-end reads were generated per sample. Reads were filtered and processed using Trimmomatic and mapped to the porcine genome assembly Sscrofa10.2 with TopHat2. Mapped reads were counted by the use of QuasR qCount based on the current National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/) GFF3 annotation file. Statistical analysis of count data was performed with the BioConductor R (https://www.bioconductor.org/) package DESEqn 2. At all 3 stages, we found 7 Y-linked transcripts that were highly expressed in male embryos (EIF2S3, EIF1AY, LOC100624590, LOC100625207, LOC100624329, LOC102162178, LOC100624937). On the other hand, 47 X-linked transcripts showed increased expression in female blastocysts, most of them at all 3 time points. However, a small number of genes (DDX3X, LAMP2, and RPS6KA3) were more highly expressed in females at Days 8 and 10 but more highly expressed in males at Day 12. Three X-linked genes (OFD1, KAL1, and LOC100525092) were more highly expressed in male embryos, although only at a low fold change of 1.2 to 1.4. Furthermore, expression of 8 transcripts located on autosomes was higher in females. In conclusion, our study expands the current knowledge of sex-specific gene expression in 8- to 12-day-old porcine blastocysts, a critical time period during pre-implantation embryo development.

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