X chromosome gene dosage compensation in female mammals

1993 ◽  
Vol 4 (2) ◽  
pp. 129-139 ◽  
Author(s):  
Giuseppe Borsani ◽  
Andrea Ballabio
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Dosage ◽  
Chromosome Gene

scholarly journals On the Mode of Gene-Dosage Compensation in Drosophila

Genetics ◽  
1997 ◽  
Vol 145 (3) ◽  
pp. 729-736
Author(s):  
Irina Arkhipova ◽  
Jingjing Li ◽  
Matthew Meselson
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Dosage ◽  
Gene Activity ◽  
Gene Copy ◽  
Drosophila Pseudoobscura ◽  
A Site ◽  
Reduced Activity ◽  
Per Gene

A procedure is described for determining the mode and magnitude of gene-dosage compensation of transformed genes. It involves measurement of the ratio of the activity of a gene inserted at X-linked sites to the activity of the same gene inserted at autosomal sites. Applying the procedure to the Drosophila pseudoobscura Hsp82 gene inserted at ectopic sites in D. melanogaster and taking gene activity as proportional to the amount of transcript per gene copy, we conclude that (1) in both adults and larvae the gene is not compensated at autosomal sites or at a site in β-heterochromatin at the base of the X chromosome and is fully compensated at euchromatic X-chromosomal sites; (2) inappropriate normalization is responsible for a claim that the gene is compensated at autosomal sites; and (3) the observed compensation operates mainly or entirely by heightened activity of X-linked genes in males, rather than by reduced activity in females.

scholarly journals Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

2021 ◽  
Vol 4 (9) ◽  
pp. e202000996
Author(s):  
Claudia Isabelle Keller Valsecchi ◽  
Eric Marois ◽  
M Felicia Basilicata ◽  
Plamen Georgiev ◽  
Asifa Akhtar
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Dosage ◽  
Histone H4 ◽  
Ecological Constraints ◽  
Evolutionary Trajectory ◽  
X Chromosomes ◽  
Deleterious Gene ◽  
Msl Complex ◽  
High Degree

Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.

scholarly journals X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells

2020 ◽  
Vol 160 (6) ◽  
pp. 283-294 ◽  
Author(s):  
Paola Rebuzzini ◽  
Maurizio Zuccotti ◽  
Silvia Garagna
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Pluripotent Stem Cells ◽  
Mammalian Cells ◽  
Gene Dosage ◽  
X Chromosome Inactivation ◽  
Preimplantation Development ◽  
Chromosome Inactivation ◽  
Transcriptional Gene Silencing

X dosage compensation between XX female and XY male mammalian cells is achieved by a process known as X-chromosome inactivation (XCI). XCI initiates early during preimplantation development in female cells, and it is subsequently stably maintained in somatic cells. However, XCI is a reversible process that occurs in vivo in the inner cell mass of the blastocyst, in primordial germ cells or in spermatids during reprogramming. Erasure of transcriptional gene silencing can occur though a mechanism named X-chromosome reactivation (XCR). XCI and XCR have been substantially deciphered in the mouse, whereas they still remain debated in the human. In this review, we summarized the recent advances in the knowledge of X-linked gene dosage compensation during mouse and human preimplantation development and in pluripotent stem cells.

scholarly journals Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity

2017 ◽  
Vol 26 (7) ◽  
pp. 1219-1229 ◽  
Author(s):  
Kirstine Belling ◽  
Francesco Russo ◽  
Anders B. Jensen ◽  
Marlene D. Dalgaard ◽  
David Westergaard ◽  
...  
Keyword(s):  
X Chromosome ◽  
Klinefelter Syndrome ◽  
Gene Dosage ◽  
Altered Protein ◽  
Chromosome Gene ◽  
Protein Interactome

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 The Effect of Hybridization on Dosage Compensation in Member Species of the Anopheles gambiae Species Complex

2018 ◽  
Author(s):  
Kevin C. Deitz ◽  
Willem Takken ◽  
Michel A. Slotman
Keyword(s):  
Sex Determination ◽  
Anopheles Gambiae ◽  
Y Chromosome ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosomes ◽  
Species Complex ◽  
F1 Hybrids ◽  
Chromosome Gene ◽  
Heterogametic Sex

AbstractDosage compensation has evolved in concert with Y-chromosome degeneration in many taxa that exhibit heterogametic sex chromosomes. Dosage compensation overcomes the biological challenge of a "half dose" of X chromosome gene transcripts in the heterogametic sex. The need to equalize gene expression of a hemizygous X with that of autosomes arises from the fact that the X chromosomes retain hundreds of functional genes that are actively transcribed in both sexes and interact with genes expressed on the autosomes. Sex determination and heterogametic sex chromosomes have evolved multiple times in Diptera, and in each case the genetic control of dosage compensation is tightly linked to sex determination. In the Anopheles gambiae species complex (Culicidae), maleness is conferred by the Y-chromosome gene Yob, which despite its conserved role between species is polymorphic in its copy number between them. Previous work demonstrated that male An. gambiae s.s. males exhibit complete dosage compensation in pupal and adult stages. In the present study we have extended this analysis to three sister species in the An. gambiae complex: An. coluzzii, An. arabiensis, and An. quadriannulatus. In addition, we analyzed dosage compensation in bi-directional F1 hybrids between these species to determine if hybridization results in the mis-regulation and disruption of dosage compensation. Our results confirm that dosage compensation operates in the An. gambiae species complex through the hyper-transcription of the male X chromosome. Additionally, dosage compensation in hybrid males does not differ from parental males, indicating that hybridization does not result in the mis-regulation of dosage compensation.

More about the tabby mouse and about the Lyon hypothesis

Development ◽  
1966 ◽  
Vol 16 (3) ◽  
pp. 569-590
Author(s):  
Hans Grüneberg
Keyword(s):  
Single Dose ◽  
Embryonic Development ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Dosage ◽  
The Body ◽  
Double Dose ◽  
Inactive X Chromosome ◽  
Lyon Hypothesis ◽  
Mammalian Female

Autosomal genes are present in duplicate in the body cells of both sexes. Genes carried in the X-chromosome are present in double dose in the mammalian female, but only in single dose in the mammalian male. Despite this disparity in gene dosage, the phenotypic effects of such genes are generally the same in homozygous and in hemizygous condition. To bring about this situation, some kind of ‘dosage compensation’ is required. A possible mechanism of dosage compensation in mammals which has been widely discussed in recent years is the ‘inactive-X-chromosome’ or ‘single-active X-chromosome’ hypothesis. As originally put forward by Lyon (1961, 1962), this postulates that during embryonic development, either the maternal or the paternal X-chromosome of the female is inactivated. Inactivation happens at random and is irreversible; it thus persists in the descendants of the cell in which it has occurred.

scholarly journals X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome

2016 ◽  
Vol 174 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Elodie Fiot ◽  
Delphine Zenaty ◽  
Priscilla Boizeau ◽  
Jeremy Haigneré ◽  
Sophie Dos Santos ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
Multiple Testing ◽  
Adult Height ◽  
Gene Dosage ◽  
Postnatal Growth ◽  
Target Height ◽  
Anthropometric Parameters ◽  
Gh Treatment ◽  
Chromosome Gene

ObjectiveShort stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment.DesignWe conducted a national observational multicenter study.MethodsBirth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%).ResultsBirth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3–11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0–21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome.ConclusionThese data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.

scholarly journals Clinical Epigenetic Therapies Disrupt Sex Chromosome Dosage Compensation in Human Female Cells

2018 ◽  
Vol 2 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Agnieszka I. Laskowski ◽  
Danielle A. Fanslow ◽  
Erica D. Smith ◽  
Steven T. Kosak
Keyword(s):  
Small Molecule ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Gene Dosage ◽  
X Inactivation ◽  
Epigenetic Mechanism ◽  
Human Female ◽  
Healthy Human ◽  
Inactivation Center

Sex chromosome gene dosage compensation is required to ensure equivalent levels of X-linked gene expression between males (46, XY) and females (46, XX). To achieve similar expression, X-chromosome inactivation (XCI) is initiated in female cells during early stages of embryogenesis. Within each cell, either the maternal or paternal X chromosome is selected for whole chromosome transcriptional silencing, which is initiated and maintained by epigenetic and chromatin conformation mechanisms. With the emergence of small-molecule epigenetic inhibitors for the treatment of disease, such as cancer, the epigenetic mechanism underlying XCI may be inadvertently targeted. Here, we test 2 small-molecule epigenetic inhibitors being used clinically, GSK126 (a histone H3 lysine 27 methyltransferase inhibitor) and suberoylanilide hydroxamic acid (a histone deacetylase inhibitor), on their effects of the inactive X (Xi) in healthy human female fibroblasts. The combination of these modifiers, at subcancer therapeutic levels, leads to the inability to detect the repressive H3K27me3 modification characteristic of XCI in the majority of the cells. Importantly, genes positioned near the X-inactivation center ( Xic), where inactivation is initiated, exhibit robust expression with treatment of the inhibitors, while genes located near the distal ends of the X chromosome intriguingly exhibit significant downregulation. These results demonstrate that small-molecule epigenetic inhibitors can have profound consequences on XCI in human cells, and they underscore the importance of considering gender when developing and clinically testing small-molecule epigenetic inhibitors, in particular those that target the well-characterized mechanisms of X inactivation.

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