Asynchronous Replication Timing: A Mechanism for Monoallelic Choice During Development

Bergman, Yehudit; Simon, Itamar; Cedar, Howard

doi:10.3389/fcell.2021.737681

Cited by 4 publications

(5 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We and others previously reported that ASRT of random mono-allelic genes is coordinated with other random mono-allelic genes on the same chromosome, suggesting that there is a chromosome-wide system that coordinates replication asynchrony of random AEI genes 4 , 9 , 28 , 32 , 51 . More recently, the asynchrony associated with random AEI genes in mouse pre-B cells was proposed to be coordinated on all autosomes, resulting in only two “mirror-image” patterns of asynchronous replication 52 , 53 . For the analysis of coordination at ASRT regions utilizing Repli-seq, we first defined ASRT regions as outliers on the distribution (SD > 1) of the difference between haplotype 1 and haplotype 2 RT profiles within each EB3_2 clone.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability

et al. 2022

View full text Add to dashboard Cite

ASARs are long noncoding RNA genes that control replication timing of entire human chromosomes in cis. The three known ASAR genes are located on human chromosomes 6 and 15, and are essential for chromosome integrity. To identify ASARs on all human chromosomes we utilize a set of distinctive ASAR characteristics that allow for the identification of hundreds of autosomal loci with epigenetically controlled, allele-restricted behavior in expression and replication timing of coding and noncoding genes, and is distinct from genomic imprinting. Disruption of noncoding RNA genes at five of five tested loci result in chromosome-wide delayed replication and chromosomal instability, validating their ASAR activity. In addition to the three known essential cis-acting chromosomal loci, origins, centromeres, and telomeres, we propose that all mammalian chromosomes also contain “Inactivation/Stability Centers” that display allele-restricted epigenetic regulation of protein coding and noncoding ASAR genes that are essential for replication and stability of each chromosome.

show abstract

Section: Resultsmentioning

confidence: 99%

Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability

et al. 2022

View full text Add to dashboard Cite

show abstract

“…We and others previously reported that ASRT of random mono-allelic genes is coordinated with other random mono-allelic genes on the same chromosome, suggesting that there is a chromosome-wide system that coordinates replication asynchrony of random AEI genes 4,9,28,32,52 . More recently, the asynchrony associated with random AEI genes in mouse pre-B cells was proposed to be coordinated on all autosomes, resulting in only two “mirror-image” patterns of asynchronous replication 53,54 . For the analysis of coordination at ASRT regions utilizing Repli-seq, we first defined ASRT regions as outliers on the distribution (SD >1) of the difference between haplotype 1 and haplotype 2 RT profiles within each EB3_2 clone.…”

Section: Resultsmentioning

confidence: 99%

“…More recently, the asynchrony associated with random AEI genes in mouse pre-B cells was proposed to be coordinated on all autosomes, resulting in only two "mirror-image" patterns of asynchronous replication 53,54 . For the analysis of coordination at ASRT regions utilizing Repliseq, we first defined ASRT regions as outliers on the distribution (SD >1) of the difference between haplotype 1 and haplotype 2 RT profiles within each EB3_2 clone.…”

Section: Asynchronous Replication Can Occur At Rtqtl and Lacks Coordi...mentioning

confidence: 99%

Epigenetic Control of Hundreds of Chromosome-Associated lncRNA Genes Essential for Replication and Stability

Heskett

Vouzas

et al. 2022

Preprint

View full text Add to dashboard Cite

ASARs are long noncoding RNA genes that control replication timing of entire human chromosomes in cis. The three known ASAR genes are located on human chromosomes 6 and 15, and are essential for chromosome integrity. To identify ASARs on all human chromosomes we utilized a set of distinctive ASAR characteristics that allowed for the identification of hundreds of autosomal loci with epigenetically controlled, allele-restricted behavior in expression and replication timing of coding and noncoding genes, and is distinct from genomic imprinting. Disruption of noncoding RNA genes at five of five tested loci resulted in chromosome-wide delayed replication and chromosomal instability, validating their ASAR activity. In addition to the three known essential cis-acting chromosomal loci, origins, centromeres, and telomeres, we propose that all mammalian chromosomes also contain “Inactivation/Stability Centers” that display allele-restricted epigenetic regulation of protein coding and noncoding ASAR genes that are essential for replication and stability of each chromosome.

show abstract

“…The substantial number of loci with putative parental allele-specific methylation allowed us to characterize these regions, revealing enrichment for regulatory regions (bearing chromatin marks of enhancers and promoters) and for polycomb targets, consistent with a role in regulation of monoallelic expression of nearby genes. Putative imprinted loci also tend to reside near origins of DNA replication, raising the testable hypothesis that parent-of-origin dependent asynchronous DNA replication controls parent-of-origin-dependent allele-specific methylation 58,59 . Further analysis is required to investigate the relationship between cell-type-specific allele-specific methylation and cell-type-specific asynchronous DNA replication.…”

Section: Discussionmentioning

confidence: 99%

Atlas of imprinted and allele-specific DNA methylation in the human body

Rosenski,

Peretz,

Magenheim

et al. 2024

Preprint

View full text Add to dashboard Cite

Allele-specific DNA methylation, determined genetically or epigenetically, is involved in gene regulation and underlies multiple pathologies. Yet, our knowledge of this phenomenon is partial, and largely limited to blood lineages. Here, we present a comprehensive atlas of allele-specific DNA methylation, using deep whole-genome sequencing across 39 normal human cell types. We identified 325k genomic regions, covering 6% of the genome and containing 11% of all CpG sites, that show a bimodal distribution of methylated and unmethylated molecules. In 34K of these regions, genetic variations at individual alleles segregate with methylation patterns, thus validating allele-specific methylation. We also identified 460 regions showing parentally-imprinted methylation, the majority of which were not previously reported. Surprisingly, sequence-dependent and parent-dependent methylation patterns are often restricted to specific cell types, revealing unappreciated variation in the human allele-specific methylation across the human body. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types.

show abstract

Asynchronous Replication Timing: A Mechanism for Monoallelic Choice During Development

Cited by 4 publications

References 77 publications

Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability

Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability

Epigenetic Control of Hundreds of Chromosome-Associated lncRNA Genes Essential for Replication and Stability

Atlas of imprinted and allele-specific DNA methylation in the human body

Contact Info

Product

Resources

About