scholarly journals LINE-1 transcription in round spermatids is associated with accretion of 5-carboxylcytosine in their open reading frames

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Martin J. Blythe ◽  
Ayhan Kocer ◽  
Alejandro Rubio-Roldan ◽  
Tom Giles ◽  
Abdulkadir Abakir ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Open Reading Frames ◽  
Dna Modification ◽  
Direct Role ◽  
Male And Female ◽  
Dna Modifications ◽  
Fine Regulation ◽  
Active Transcription ◽  
Methylation Patterns ◽  
Reading Frames

AbstractChromatin of male and female gametes undergoes a number of reprogramming events during the transition from germ cell to embryonic developmental programs. Although the rearrangement of DNA methylation patterns occurring in the zygote has been extensively characterized, little is known about the dynamics of DNA modifications during spermatid maturation. Here, we demonstrate that the dynamics of 5-carboxylcytosine (5caC) correlate with active transcription of LINE-1 retroelements during murine spermiogenesis. We show that the open reading frames of active and evolutionary young LINE-1s are 5caC-enriched in round spermatids and 5caC is eliminated from LINE-1s and spermiogenesis-specific genes during spermatid maturation, being simultaneously retained at promoters and introns of developmental genes. Our results reveal an association of 5caC with activity of LINE-1 retrotransposons suggesting a potential direct role for this DNA modification in fine regulation of their transcription.

Different genomic DNA methylation patterns between male and female adults of white-backed planthoppers Sogatella furcifera

2014 ◽  
Vol 17 (4) ◽  
pp. 917-921
Author(s):  
Mei Zhang ◽  
Jia-Lin Chen ◽  
Xiao-Sui Zhou ◽  
Shi-Ke Liang ◽  
Guang-Hong Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genomic Dna ◽  
Sogatella Furcifera ◽  
Male And Female ◽  
Methylation Patterns

Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1807-1817 ◽  
Author(s):  
Jiyoung Lee ◽  
Kimiko Inoue ◽  
Ryuichi Ono ◽  
Narumi Ogonuki ◽  
Takashi Kohda ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genomic Imprinting ◽  
Nuclear Transfer ◽  
Monoallelic Expression ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Male And Female ◽  
Imprinted Gene ◽  
Methylation Patterns

Genomic imprinting is an epigenetic mechanism that causes functional differences between paternal and maternal genomes, and plays an essential role in mammalian development. Stage-specific changes in the DNA methylation patterns of imprinted genes suggest that their imprints are erased some time during the primordial germ cell (PGC) stage, before their gametic patterns are re-established during gametogenesis according to the sex of individuals. To define the exact timing and pattern of the erasure process, we have analyzed parental-origin-specific expression of imprinted genes and DNA methylation patterns of differentially methylated regions (DMRs) in embryos, each derived from a single day 11.5 to day 13.5 PGC by nuclear transfer. Cloned embryos produced from day 12.5 to day 13.5 PGCs showed growth retardation and early embryonic lethality around day 9.5. Imprinted genes lost their parental-origin-specific expression patterns completely and became biallelic or silenced. We confirmed that clones derived from both male and female PGCs gave the same result, demonstrating the existence of a common default state of genomic imprinting to male and female germlines. When we produced clone embryos from day 11.5 PGCs, their development was significantly improved, allowing them to survive until at least the day 11.5 embryonic stage. Interestingly, several intermediate states of genomic imprinting between somatic cell states and the default states were seen in these embryos. Loss of the monoallelic expression of imprinted genes proceeded in a step-wise manner coordinated specifically for each imprinted gene. DNA demethylation of the DMRs of the imprinted genes in exact accordance with the loss of their imprinted monoallelic expression was also observed. Analysis of DNA methylation in day 10.5 to day 12.5 PGCs demonstrated that PGC clones represented the DNA methylation status of donor PGCs well. These findings provide strong evidence that the erasure process of genomic imprinting memory proceeds in the day 10.5 to day 11.5 PGCs, with the timing precisely controlled for each imprinted gene. The nuclear transfer technique enabled us to analyze the imprinting status of each PGC and clearly demonstrated a close relationship between expression and DNA methylation patterns and the ability of imprinted genes to support development.

scholarly journals Role of the Promoter in Maintaining Transcriptionally Active Chromatin Structure and DNA Methylation Patterns In Vivo

2003 ◽  
Vol 23 (12) ◽  
pp. 4150-4161 ◽  
Author(s):  
Sung-Hae Lee Kang ◽  
Christine Mione Kiefer ◽  
Thomas P. Yang
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Dnase I ◽  
Dnase I Hypersensitivity ◽  
Translation Start ◽  
Dnase I Sensitivity ◽  
Active Transcription ◽  
Methylation Patterns

ABSTRACT Establishment and maintenance of differential chromatin structure between transcriptionally competent and repressed genes are critical aspects of transcriptional regulation. The elements and mechanisms that mediate formation and maintenance of these chromatin states in vivo are not well understood. To examine the role of the promoter in maintaining chromatin structure and DNA methylation patterns of the transcriptionally active X-linked HPRT locus, 323 bp of the endogenous human HPRT promoter (from position −222 to +102 relative to the translation start site) was replaced by plasmid sequences by homologous recombination in cultured HT-1080 male fibrosarcoma cells. The targeted cells, which showed no detectable HPRT transcription, were then assayed for effects on DNase I hypersensitivity, general DNase I sensitivity, and DNA methylation patterns across the HPRT locus. In cells carrying the deletion, significantly diminished DNase I hypersensitivity in the 5′ flanking region was observed compared to that in parental HT-1080 cells. However, general DNase I sensitivity and DNA methylation patterns were found to be very similar in the mutated cells and in the parental cells. These findings suggest that the promoter and active transcription play a relatively limited role in maintaining transcriptionally potentiated epigenetic states.

scholarly journals Examining age-dependent DNA methylation patterns and gene expression in the male and female hippocampus

2021 ◽  
Author(s):  
Carlene Chinn ◽  
Honglei Ren ◽  
Julien Morival ◽  
Qing Nie ◽  
Marcelo A. Wood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Male And Female ◽  
Age Dependent ◽  
Methylation Patterns

scholarly journals Chromatin structure and its chemical modifications regulate the ubiquitin ligase substrate selectivity of UHRF1

2018 ◽  
Vol 115 (35) ◽  
pp. 8775-8780 ◽  
Author(s):  
Robert M. Vaughan ◽  
Bradley M. Dickson ◽  
Matthew F. Whelihan ◽  
Andrea L. Johnstone ◽  
Evan M. Cornett ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ubiquitin Ligase ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Substrate Selectivity ◽  
Rigorous Analysis ◽  
Dna Oligonucleotides ◽  
Ubiquitin Ligase Activity ◽  
Dna Modifications ◽  
Methylation Patterns

Mitotic inheritance of DNA methylation patterns is facilitated by UHRF1, a DNA- and histone-binding E3 ubiquitin ligase that helps recruit the maintenance DNA methyltransferase DNMT1 to replicating chromatin. The DNA methylation maintenance function of UHRF1 is dependent on its ability to bind chromatin, where it facilitates monoubiquitination of histone H3 at lysines 18 and 23, a docking site for DNMT1. Because of technical limitations, this model of UHRF1-dependent DNA methylation inheritance has been constructed largely based on genetics and biochemical observations querying methylated DNA oligonucleotides, synthetic histone peptides, and heterogeneous chromatin extracted from cells. Here, we construct semisynthetic mononucleosomes harboring defined histone and DNA modifications and perform rigorous analysis of UHRF1 binding and enzymatic activity with these reagents. We show that multivalent engagement of nucleosomal linker DNA and dimethylated lysine 9 on histone H3 directs UHRF1 ubiquitin ligase activity toward histone substrates. Notably, we reveal a molecular switch, stimulated by recognition of hemimethylated DNA, which redirects UHRF1 ubiquitin ligase activity away from histones in favor of robust autoubiquitination. Our studies support a noncompetitive model for UHRF1 and DNMT1 chromatin recruitment to replicating chromatin and define a role for hemimethylated linker DNA as a regulator of UHRF1 ubiquitin ligase substrate selectivity.

scholarly journals Extensive N4 Cytosine Methylation is Essential for Marchantia Sperm Function

2021 ◽  
Author(s):  
James Walker ◽  
Jingyi Zhang ◽  
Yalin Liu ◽  
Martin Vickers ◽  
Liam Dolan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cytosine Methylation ◽  
Marchantia Polymorpha ◽  
Sperm Function ◽  
Dna Modification ◽  
Entire Genome ◽  
New Family ◽  
Dna Modifications ◽  
Eukaryotic Dna ◽  
Second Wave

Abstract4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance, and even presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwort Marchantia polymorpha involves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC), a well-known eukaryotic DNA modification, expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC is catalyzed by two novel methyltransferases (MpDN4MT1a and MpDN4MT1b) specifically expressed during late spermiogenesis. Deletion of MpDN4MT1s eliminates 4mC, alters the sperm transcriptome, and produces sperm with swimming defects. Our results reveal extensive 4mC in a eukaryote and define a new family of eukaryotic methyltransferases, thereby expanding the repertoire of functional eukaryotic DNA modifications.

scholarly journals Age and mortality associated DNA methylation patterns on the X-chromosome in male and female samples

2019 ◽  
Author(s):  
Shuxia Li ◽  
Jesper B. Lund ◽  
Jan Baumbach ◽  
Kaare Christensen ◽  
Jonas Mengel-From ◽  
...  
Keyword(s):  
Dna Methylation ◽  
X Chromosome ◽  
Association Studies ◽  
Male And Female ◽  
Chromosome 20 ◽  
Age Related ◽  
Large Numbers ◽  
Genome Wide ◽  
Lothian Birth Cohort ◽  
Methylation Patterns

AbstractBackgroundMultiple epigenetic association studies on human aging have been performed reporting large numbers of sites differentially methylated across ages on the autosomal chromosomes. The X-chromosome has been studied little, due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation in females. Based on large collections of genome-wide DNA methylation data on two Danish cohorts of identical twins (mean ages, 66 and 79 years) and the Lothian Birth Cohort 1921 (mean age 79 years), we conducted a chromosome-wide association analysis on male and female samples separately with equal sample sizes to discover age-dependent X-linked DNA methylation patterns using chromosome 20 with about same number of CpGs analysed as an autosomal reference, and compare the age-related changes in DNA methylation between the two sexes. In addition, age-related methylation sites were assessed for their associations with mortality.ResultsWe identified more age-related DNA methylation sites (FDR<0.05) in females than in males. Among them, predominantly more sites were hypermethylated in the older as compared with the younger cohorts, a pattern similar to that observed on chromosome 20. Among the age-related sites, 13 CpGs in males and 24 CpGs in females were found significant (FDR<0.05) in all cohorts. Survival analysis showed that there are more age-methylated CpGs that contribute to reduce mortality than those that increase mortality in male but not in female samples.ConclusionThe X-chromosome displays significant age-and sex-dependent methylation patterns which might be differentially associated with mortality in the two sexes.

scholarly journals Transcription Profiling-Based Identification ofStaphylococcus aureus Genes Regulated by the agrand/or sarA Loci

2001 ◽  
Vol 183 (24) ◽  
pp. 7341-7353 ◽  
Author(s):  
P. M. Dunman ◽  
E. Murphy ◽  
S. Haney ◽  
D. Palacios ◽  
G. Tucker-Kellogg ◽  
...  
Keyword(s):  
Stationary Phases ◽  
Protein A ◽  
Open Reading Frames ◽  
Dependent Manner ◽  
Biological Processes ◽  
Transcription Profiling ◽  
Direct Role ◽  
Custom Made ◽  
Regulatory Cascades ◽  
Reading Frames

ABSTRACT The advent of transcription profiling technologies has provided researchers with an unprecedented ability to study biological processes. Accordingly, a custom-made Affymetrix GeneChip, constituting >86% of the Staphylococcus aureus genome, was used to identify open reading frames that are regulated by agrand/or SarA, the two best-studied regulators of the organism's virulence response. RNA extracted from wild-type cells andagr, sarA, and agr sarAmutant cells in the early-, mid-, and late-log and stationary phases of growth was analyzed. Open reading frames with transcription patterns expected of genes either up- or downregulated in anagr- and/or SarA-dependent manner were identified. Oligonucleotide microarray and Northern blot analyses confirmed that the transcription of several known virulence genes, includinghla (alpha-toxin) and spa (protein A), is regulated by each effector and provided insights about the regulatory cascades involved in both alpha-hemolysin and protein A expression. Several putative virulence factors were also identified as regulated byagr and/or SarA. In addition, genes that are involved in several biological processes but which are difficult to reconcile as playing a direct role in the organism's pathogenesis also appeared to be regulated by each effector, suggesting that products of both the agr and the sarA locus are more-global transcription regulators than previously realized.

scholarly journals MITOCHONDRIAL SYSTEM BIOLOGY AS A WINDOW INTO DISEASES OF AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S555-S555
Author(s):  
Pinchas Cohen
Keyword(s):  
Mitochondrial Dna ◽  
Health Disparities ◽  
Native Americans ◽  
Mitochondrial Genome ◽  
System Biology ◽  
Therapeutic Potential ◽  
Open Reading Frames ◽  
New Class ◽  
Methylation Patterns ◽  
Reading Frames

Abstract We identified multiple open-reading-frames (ORFs) within the mitochondrial genome. These ORFs encode putative peptides that we call Mitochondrial-Derived-Peptides (MDPs) which represent a sub-class of a growing group of novel micro-peptides (from both mtDNA and nuclear chromosomes) that serve as signals related to cell and organismal protection and energy expenditure. We described multiple peptides including humanin, SHLPs, and MOTS-c. Exploring mtDNA methylation patterns as well as mito-transcriptomics demonstrated changes in specific ORFs/MDPs in certain diseases. We developed a modified GWAS bioinformatic technique (MiWAS) that identifies SNPs within MDPs that associate with diseases of aging. MOTS-c, and MENTSH, novel anti-obesity/diabetes MDPs, harbors mutation in Asians and Native-Americans, associated with diabetes risk. Thus, MDPs are expressed in an ethno-specific fashion and may contribute to health disparities in a manner related to relevant mitochondrial DNA SNPs. In summary, MDPs are a new class of mitochondrial-hormones that have diagnostic and therapeutic potential in human disease.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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