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 REGULATION OF GENE ACTIVITY BY DOSAGE COMPENSATION AT THE CHROMOSOMAL LEVEL IN DROSOPHILA

Genetics ◽  
1975 ◽  
Vol 79 (4) ◽  
pp. 635-647
Author(s):  
Barbara R Stewart ◽  
John R Merriam
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Normal Level ◽  
Gene Activity ◽  
Gene Copy ◽  
Activity Levels ◽  
Chromosome 2 ◽  
X Chromosomes ◽  
Proximal Half ◽  
Regulator Genes

ABSTRACT Two models of dosage compensation have been tested by the measurement of G6PD and 6PGD enzymatic specific activities in flies hyperploid for regions of the X chromosome. Females duplicated for the proximal half of the X chromosome (2½ X's) have an increased level of G6PD and a normal level of 6PGD. Females duplicated for the distal half of the X chromosome (2½ X's) have a normal level of G6PD and an increased level of 6PGD. Males bearing duplications of various segments of the X chromosome show control levels of G6PD and 6PGD, except where the duplicated region includes the structural gene for G6PD or 6PGD. These results fail to provide evidence for either the presence of discrete X-linked compensator (regulator) genes reducing the activity of other X-linked genes, or for a factor in limiting supply necessary for the transcription of all the genes on the X chromosome. Superfemales (3 X chromosomes) have the same G6PD and 6PGD activity levels as their diploid sisters. It would appear that the regulation of gene activity by dosage compensation is a chromosomal phenomenon in that the level of activity per gene copy for loci on the X chromosome is modulated in a stepwise fashion according to the total number of X chromosomes present.

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 Tissue- and Stage-Dependent Dosage Compensation on the Neo-X Chromosome in Drosophila pseudoobscura

2013 ◽  
Vol 31 (3) ◽  
pp. 614-624 ◽  
Author(s):  
Masafumi Nozawa ◽  
Nana Fukuda ◽  
Kazuho Ikeo ◽  
Takashi Gojobori
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Drosophila Pseudoobscura

scholarly journals Gene dosage compensation of rRNA transcript levels in Arabidopsis thaliana lines with reduced ribosomal gene copy number

2021 ◽  
Author(s):  
Francesca B Lopez ◽  
Antoine Fort ◽  
Luca Tadini ◽  
Aline V Probst ◽  
Marcus McHale ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Genome Editing ◽  
Dosage Compensation ◽  
Copy Number ◽  
Gene Dosage ◽  
Rrna Genes ◽  
Gene Copy ◽  
Transcript Levels ◽  
Rdna Copy ◽  
Rdna Copy Number

Abstract The 45S rRNA genes (rDNA) are amongst the largest repetitive elements in eukaryotic genomes. rDNA consists of tandem arrays of rRNA genes, many of which are transcriptionally silenced. Silent rDNA repeats may act as ‘back-up’ copies for ribosome biogenesis and have nuclear organization roles. Through Cas9-mediated genome editing in the Arabidopsis thaliana female gametophyte we reduced 45S rDNA copy number to a plateau of ∼10%. Two independent lines had rDNA copy numbers reduced by up to 90% at the T7 generation, named Low Copy Number (LCN) lines. Despite drastic reduction of rDNA copies, rRNA transcriptional rates and steady-state levels remained the same as wild type plants. Gene dosage compensation of rRNA transcript levels was associated with reduction of silencing histone marks at rDNA loci and altered Nucleolar Organiser Region 2 organization. While overall genome integrity of LCN lines appears unaffected, a chromosome segmental duplication occurred in one of the lines. Transcriptome analysis of LCN seedlings identified several shared dysregulated genes and pathways in both independent lines. Cas9 genome editing of rRNA repeats to generate LCN lines provides a powerful technique to elucidate rDNA dosage compensation mechanisms and impacts of low rDNA copy number on genome stability, development, and cellular processes.

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.

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 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.

scholarly journals DOSAGE COMPENSATION OF GENES ON THE LEFT AND RIGHT ARMS OF THE X CHROMOSOME OF DROSOPHILA PSEUDOOBSCURA AND DROSOPHILA WILLISTONI

Genetics ◽  
1974 ◽  
Vol 78 (4) ◽  
pp. 1119-1126
Author(s):  
Irene Abraham ◽  
John C Lucchesi
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
The Other ◽  
Drosophila Pseudoobscura ◽  
Chromosome 3 ◽  
Chromosome 2 ◽  
Phosphogluconate Dehydrogenase ◽  
Glycerophosphate Dehydrogenase ◽  
Left And Right ◽  
Glucose 6 Phosphate Dehydrogenase

ABSTRACT We have investigated the occurrence of dosage compensation in D. willistoni and D. pseudoobscura, two species whose X chromosome is metacentric with one arm homologous to the X and the other homologous to the left arm of chromosome 3 of D. melanogaster. Crude extracts were assayed for isocitrate dehydrogenase (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?), and α-glycerophosphate dehydrogenase (chromosome 2) in D. willistoni, and for esterase-5 (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?) and amylase (chromosome 3) in D. pseudoobscura. Our results indicate that a mechanism for dosage compensation is operative in both arms of the X chromosome of these two species.

Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs

2018 ◽  
Vol 87 (1) ◽  
pp. 323-350 ◽  
Author(s):  
Maria Samata ◽  
Asifa Akhtar
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Transcriptional Activation ◽  
Gene Dosage ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Histone H4 ◽  
Chromosome Conformation ◽  
Msl Complex ◽  
Male Specific

X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.

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