scholarly journals DNA replication timing influences gene expression level

2017 ◽  
Vol 216 (7) ◽  
pp. 1907-1914 ◽  
Author(s):  
Carolin A. Müller ◽  
Conrad A. Nieduszynski
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Temporal Order ◽  
Yeast Species ◽  
Replication Timing ◽  
Histone Genes ◽  
Cell Cycle Genes ◽  
Compensation Mechanisms ◽  
Dna Replication Timing ◽  
Eukaryotic Genomes

Eukaryotic genomes are replicated in a reproducible temporal order; however, the physiological significance is poorly understood. We compared replication timing in divergent yeast species and identified genomic features with conserved replication times. Histone genes were among the earliest replicating loci in all species. We specifically delayed the replication of HTA1-HTB1 and discovered that this halved the expression of these histone genes. Finally, we showed that histone and cell cycle genes in general are exempt from Rtt109-dependent dosage compensation, suggesting the existence of pathways excluding specific loci from dosage compensation mechanisms. Thus, we have uncovered one of the first physiological requirements for regulated replication time and demonstrated a direct link between replication timing and gene expression.

scholarly journals Aneuploidy and gene expression: is there dosage compensation?

Epigenomics ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1827-1837 ◽  
Author(s):  
Shihoko Kojima ◽  
Daniela Cimini
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Current Knowledge ◽  
Gene Dosage ◽  
Congenital Defects ◽  
Gene Products ◽  
Epigenetic Changes ◽  
Transcript Levels ◽  
Compensation Mechanisms ◽  
Additional Chromosome

Aneuploidy (i.e., abnormal chromosome number) is the leading cause of miscarriage and congenital defects in humans. Moreover, aneuploidy is ubiquitous in cancer. The deleterious phenotypes associated with aneuploidy are likely a result of the imbalance in the levels of gene products derived from the additional chromosome(s). Here, we summarize the current knowledge on how the presence of extra chromosomes impacts gene expression. We describe studies that have found a strict correlation between gene dosage and transcript levels as wells as studies that have found a less stringent correlation, hinting at the possible existence of dosage compensation mechanisms. We conclude by peering into the epigenetic changes found in aneuploid cells and outlining current knowledge gaps and potential areas of future investigation.

scholarly journals Diverse developmental strategies of X chromosome dosage compensation in eutherian mammals

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 223-233 ◽  
Author(s):  
Alexander I. Shevchenko ◽  
Elena V. Dementyeva ◽  
Irina S. Zakharova ◽  
Suren M. Zakian
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Mammalian Species ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Autosomal Gene ◽  
Mammalian Development ◽  
Compensation Mechanisms ◽  
Early Mammalian Development

In eutherian mammals, dosage compensation arose to balance X-linked gene expression between sexes and relatively to autosomal gene expression in the evolution of sex chromosomes. Dosage compensation occurs in early mammalian development and comprises X chromosome upregulation and inactivation that are tightly coordinated epigenetic processes. Despite a uniform principle of dosage compensation, mechanisms of X chromosome inactivation and upregulation demonstrate a significant variability depending on sex, developmental stage, cell type, individual, and mammalian species. The review focuses on relationships between X chromosome inactivation and upregulation in mammalian early development.

scholarly journals Mechanisms of sex determination and X-chromosome dosage compensation

Genetics ◽  
2022 ◽  
Author(s):  
Barbara J Meyer
Keyword(s):  
Gene Expression ◽  
Chromosome Number ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Molecular Mechanisms ◽  
Chromosome Counting ◽  
Developmental Defects ◽  
Chromosome Gene ◽  
Compensation Mechanisms ◽  
The Difference

Abstract Abnormalities in chromosome number have the potential to disrupt the balance of gene expression and thereby decrease organismal fitness and viability. Such abnormalities occur in most solid tumors and also cause severe developmental defects and spontaneous abortions. In contrast to the imbalances in chromosome dose that cause pathologies, the difference in X-chromosome dose used to determine sexual fate across diverse species is well tolerated. Dosage compensation mechanisms have evolved in such species to balance X-chromosome gene expression between the sexes, allowing them to tolerate the difference in X-chromosome dose. This review analyzes the chromosome counting mechanism that tallies X-chromosome number to determine sex (XO male and XX hermaphrodite) in the nematode Caenorhabditis elegans and the associated dosage compensation mechanism that balances X-chromosome gene expression between the sexes. Dissecting the molecular mechanisms underlying X-chromosome counting has revealed how small quantitative differences in intracellular signals can be translated into dramatically different fates. Dissecting the process of X-chromosome dosage compensation has revealed the interplay between chromatin modification and chromosome structure in regulating gene expression over vast chromosomal territories.

scholarly journals Rapid evolution of complete dosage compensation in Poecilia

2021 ◽  
Author(s):  
David C.H. Metzger ◽  
Benjamin A. Sandkam ◽  
Iulia Darolti ◽  
Judith E. Mank
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Sex Chromosomes ◽  
Evolutionary Dynamics ◽  
Common Ancestor ◽  
Sex Chromosome ◽  
Close Relative ◽  
Y Chromosomes ◽  
Compensation Mechanisms ◽  
The Common

ABSTRACTDosage compensation balances gene expression between the sexes in systems with diverged heterogametic sex chromosomes. Theory predicts that dosage compensation should rapidly evolve in parallel with the divergence of sex chromosomes to prevent the deleterious effects of dosage imbalances that occur as a result of sex chromosome divergence. Examples of complete dosage compensation, where gene expression of the entire sex chromosome is compensated, are rare and have only been found in relatively ancient sex chromosome systems. Consequently, very little is known about the evolutionary dynamics of complete dosage compensation systems. We recently found the first example of complete dosage compensation in a fish, Poecilia picta. We also found that the Y chromosome degraded substantially in the common ancestor of P. picta and their close relative Poecilia parae. In this study we find that P. parae also have complete dosage compensation, thus complete dosage compensation likely evolved in the short (∼3.7 my) interval after the split of the ancestor of these two species from P. reticulata, but before they diverged from each other. These data suggest that novel dosage compensation mechanisms can evolve rapidly, thus supporting the longstanding theoretical prediction that such mechanisms arise in parallel with rapidly diverging sex chromosomes.SIGNIFICANCE STATEMENTIn species with XY sex chromosomes, females (XX) have as many copies of X-linked genes compared to males (XY), leading to unbalanced expression between the sexes. Theory predicts that dosage compensation mechanisms should evolve rapidly as X and Y chromosomes diverge, but examples of complete dosage compensation in recently diverged sex chromosomes are scarce, making this theory difficult to test. Across Poeciliid species the X and Y chromosomes have recently diversified. Here we find complete dosage compensation evolved rapidly as the X and Y diverged in the common ancestor of Poecilia parae and P. picta, supporting that novel dosage compensation mechanisms can evolve rapidly in tandem with diverging sex chromosomes. These data confirm longstanding theoretical predictions of sex chromosome evolution.

scholarly journals A stitch in time: Replicate early and escape dosage compensation to express more

2017 ◽  
Vol 216 (7) ◽  
pp. 1869-1870
Author(s):  
María Gómez
Keyword(s):  
Dosage Compensation ◽  
Biological Significance ◽  
Replication Timing ◽  
Expression Levels ◽  
Cell Biol ◽  
Early Replication ◽  
Eukaryotic Genomes

The biological significance of conserved replication timing patterns in eukaryotic genomes remains a mystery. In this issue, Müller and Nieduszynski (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701061) find that early replication is a requirement for the highest expression levels of certain genes.

Replication asynchrony and differential condensation of X chromosomes in female platypus (Ornithorhynchus anatinus)

2009 ◽  
Vol 21 (8) ◽  
pp. 952 ◽  
Author(s):  
Kristen K. K. Ho ◽  
Janine E. Deakin ◽  
Megan L. Wright ◽  
Jennifer A. Marshall Graves ◽  
Frank Grützner
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Dosage Compensation ◽  
Gene Expression Analysis ◽  
Chromatin Condensation ◽  
Replication Timing ◽  
X Chromosomes ◽  
Asynchronous Replication ◽  
Y Chromosomes ◽  
Ornithorhynchus Anatinus

A common theme in the evolution of sex chromosomes is the massive loss of genes on the sex-specific chromosome (Y or W), leading to a gene imbalance between males (XY) and females (XX) in a male heterogametic species, or between ZZ and ZW in a female heterogametic species. Different mechanisms have evolved to compensate for this difference in dosage of X-borne genes between sexes. In therian mammals, one of the X chromosomes is inactivated, whereas bird dosage compensation is partial and gene-specific. In therian mammals, hallmarks of the inactive X are monoallelic gene expression, late DNA replication and chromatin condensation. Platypuses have five pairs of X chromosomes in females and five X and five Y chromosomes in males. Gene expression analysis suggests a more bird-like partial and gene-specific dosage compensation mechanism. We investigated replication timing and chromosome condensation of three of the five X chromosomes in female platypus. Our data suggest asynchronous replication of X-specific regions on X1, X3 and X5 but show significantly different condensation between homologues for X3 only, and not for X1 or X5. We discuss these results in relation to recent gene expression analysis of X-linked genes, which together give us insights into possible mechanisms of dosage compensation in platypus.

scholarly journals A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing

Blood ◽  
2013 ◽  
Vol 121 (17) ◽  
pp. 3531-3540 ◽  
Author(s):  
Apurva V. Shirodkar ◽  
Rosanne St. Bernard ◽  
Anna Gavryushova ◽  
Anna Kop ◽  
Britta J. Knight ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Endothelial Cell ◽  
Dna Replication ◽  
Replication Timing ◽  
Epigenetic Process ◽  
Key Points ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
Dna Replication Timing

Key Points Promoter DNA methylation, an epigenetic process, is functionally relevant for regulating the expression of endothelial cell–enriched genes.

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