scholarly journals Finding a Balance: How Diverse Dosage Compensation Strategies Modify Histone H4 to Regulate Transcription

2012 ◽  
Vol 2012 ◽  
pp. 1-12
Author(s):  
Michael B. Wells ◽  
Györgyi Csankovszki ◽  
Laura M. Custer

Dosage compensation balances gene expression levels between the sex chromosomes and autosomes and sex-chromosome-linked gene expression levels between the sexes. Different dosage compensation strategies evolved in different lineages, but all involve changes in chromatin. This paper discusses our current understanding of how modifications of the histone H4 tail, particularly changes in levels of H4 lysine 16 acetylation and H4 lysine 20 methylation, can be used in different contexts to either modulate gene expression levels twofold or to completely inhibit transcription.

2020 ◽  
Author(s):  
T Chae ◽  
A Harkess ◽  
RC Moore

ABSTRACTOne evolutionary path from hermaphroditism to dioecy is via a gynodioecious intermediate. The evolution of dioecy may also coincide with the formation of sex chromosomes that possess sex-determining loci that are physically linked in a region of suppressed recombination. Dioecious papaya (Carica papaya) has an XY chromosome system, where the presence of a Y chromosome determines males. However, in cultivation, papaya is gynodioecious, due to the conversion of the male Y chromosome to a hermaphroditic Yh chromosome during its domestication. We investigated gene expression linked to the X, Y, and Yh chromosomes at different floral developmental stages in order to identify differentially expressed genes (DEGs) that may be involved in the sexual reversion of males to hermaphrodites. We identified 309 sex-biased genes found on the sex chromosomes, most of which are found in the pseudoautosomal regions (PARs). Female (XX) expression in the sex determining region (SDR) was almost double that of X-linked expression in males (XY) and hermaphrodites (XYh), which rules out dosage compensation for most sex-linked gene; although, an analysis of hemizygous X-linked loci found evidence of partial dosage compensation. Furthermore, we identified a potential candidate gene associated with both sex determination and the transition to hermaphroditism, a homolog of the MADS-box protein SHORT VEGETATIVE PHASE (SVG).


2018 ◽  
Author(s):  
Alyssa N. Kruger ◽  
Quinn Ellison ◽  
Michele A. Brogley ◽  
Emma R. Gerlinger ◽  
Jacob L. Mueller

AbstractLarge (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families (≥2 gene copies) expressed exclusively in post-meiotic testicular germ cells, at a time when most single-copy sex-linked genes are transcriptionally repressed. This distinct expression pattern led to the hypothesis that containment within palindrome structures or having ≥2 gene enables post-meiotic gene expression. We tested these two hypotheses by using CRISPR to precisely engineer large (10’s of kb) inversions and deletions of X chromosome palindrome arms for two regions carrying the mouse 4930567H17Rik and Mageb5 gene families. We found that 4930567H17Rik and Mageb5 gene expression is unaffected in mice carrying palindrome arm inversions, suggesting that palindromic structure is not important for mediating palindrome-associated gene expression. We also found that 4930567H17Rik and Mageb5 gene expression is reduced by half in mice carrying palindrome arm deletions, allowing us to test whether palindrome-associated genes are sensitive to reduced expression levels resulting in spermatogenic defects. Male mice carrying palindrome arm deletions of 4930567H17Rik or Mageb5, however, are fertile, have normal testis histology, and show no aberrations in spermatogenic cell population frequencies via FACS quantification. Together, these findings suggest that large palindromic structures on the sex chromosomes are not necessary for their associated genes to evade post-meiotic transcriptional repression and that these genes are not sensitive to reduced expression levels. Large sex chromosome palindromes may thus be important for other reasons, such as the long-term evolutionary stability of their associated gene families.


2021 ◽  
Author(s):  
David C.H. Metzger ◽  
Benjamin A. Sandkam ◽  
Iulia Darolti ◽  
Judith E. Mank

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.


2021 ◽  
Author(s):  
Leah F. Rosin ◽  
Yang Chen ◽  
Elissa P Lei

Interphase chromatin is organized precisely to facilitate accurate gene expression. The structure-function relationship of chromatin is epitomized in sex chromosome dosage compensation (DC), where sex-linked gene expression is balanced between males and females via sex-specific alterations to 3D chromosome structure. Studies in ZW-bearing species suggest that DC is absent or incomplete in most lineages except butterflies and moths, where male (ZZ) chZ expression is reduced by half to equal females (ZW). However, whether one chZ is inactivated (as in mammals) or both are partially repressed (as in C. elegans) is unknown. Using Oligopaints in the silkworm, Bombyx mori, we visualize autosome and chZ organization in somatic cells from both sexes for the first time. We find that B. mori interphase chromosomes are highly compact relative to Drosophila chromosomes. Importantly, we show that in B. mori males, both chZs are similar in size and shape and are more compact than autosomes or the female chZ after DC establishment, suggesting that both male chZs are partially and equally downregulated. We also find that in the early stages of DC, the female chZ repositions toward the nuclear center concomitant with increased Z-linked gene expression, revealing the first non-sequencing-based support for Ohno's hypothesis. These studies represent the first visualization of interphase genome organization and chZ structure in Lepidoptera. We uncover striking similarities between DC in B. mori and C. elegans, despite these lineages harboring evolutionarily distinct sex chromosomes (ZW/XY), suggesting convergent evolution of DC mechanisms and a possible role for holocentricity in DC evolution.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Liu ◽  
Jennifer Han ◽  
Anupma Sharma ◽  
Ching Man Wai ◽  
Ray Ming ◽  
...  

AbstractSex chromosome evolution results in the disparity in gene content between heterogametic sex chromosomes and creates the need for dosage compensation to counteract the effects of gene dose imbalance of sex chromosomes in males and females. It is not known at which stage of sex chromosome evolution dosage compensation would evolve. We used global gene expression profiling in male and female papayas to assess gene expression patterns of sex-linked genes on the papaya sex chromosomes. By analyzing expression ratios of sex-linked genes to autosomal genes and sex-linked genes in males relative to females, our results showed that dosage compensation was regulated on a gene-by-gene level rather than whole sex-linked region in papaya. Seven genes on the papaya X chromosome exhibited dosage compensation. We further compared gene expression ratios in the two evolutionary strata. Y alleles in the older evolutionary stratum showed reduced expression compared to X alleles, while Y alleles in the younger evolutionary stratum showed elevated expression compared to X alleles. Reduced expression of Y alleles in the older evolutionary stratum might be caused by accumulation of deleterious mutations in regulatory regions or transposable element-mediated methylation spreading. Most X-hemizygous genes exhibited either no or very low expression, suggesting that gene silencing might play a role in maintaining transcriptional balance between females and males.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.


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