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 inactivation: dosage compensation of genes or heterochromatin?

2019 ◽  
pp. 75-87
Author(s):  
AI Ibraimov
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Gene Dosage ◽  
Alternative Hypothesis ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Inactive X Chromosome ◽  
Mammalian Female

X-chromosome inactivation (XCI) is the process by which one of two X chromosomes in mammalian female cells is inactivated. The DNA of the inactive X chromosome is packaged in transcriptionally inactive heterochromatin. It is generally accepted that XCI have evolved to enable dosage compensation in mammals as a way to equalize X-linked gene expression between XX and XY individuals. However, there remain several controversial issues regarding the causes of XCI. The most important of them, why dosage compensation of genes? An alternative hypothesis is discussed that XCI is caused by dose compensation for heterochromatin, rather than genes, in the genome of female mammals due to the lack of a sex chromosome in their karyotype with a large constitutive heterochromatin block, as in Y chromosome in males. It is for this reason that heterochromatinization of the euchromatin regions of one of the X chromosomes occurs. The biological meaning of heterochromatinization is to increase the density of condensed chromatin (??) around the interphase nucleus, responsible for removing excess heat from the nucleus into the cytoplasm, since the compaction of ?? depends on the amount of heterochromatin. The consequence of this process is the inactivation of genes that were in the area of heterochromatinization of the X chromosome. Keywords: X-chromosome inactivation; Lyonization; Gene dosage compensation; Heterochromatin dosage compensation; Cell thermoregulation

scholarly journals Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1114
Author(s):  
Ali Youness ◽  
Charles-Henry Miquel ◽  
Jean-Charles Guéry
Keyword(s):  
Autoimmune Diseases ◽  
X Chromosome ◽  
Gene Dosage ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Female Sex Hormones ◽  
Inactive X Chromosome ◽  
Immune Related Genes ◽  
Female Specific

Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.

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 Gene action in the mammalian X-chromosome

1967 ◽  
Vol 9 (3) ◽  
pp. 343-357 ◽  
Author(s):  
Hans Grüneberg
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Action ◽  
X Chromosomes ◽  
Independent Evidence ◽  
Partial Inhibition ◽  
Lyon Hypothesis ◽  
New Hypothesis

Contrary to opinions expressed by various authors, the phenotype of heterozygotes for mammalian sex-linked genes gives no support for the Lyon hypothesis (L.H.). Evidence, mainly from the mouse, shows that in such heterozygotes, both alleles act together as in autosomal genes.In the present paper, it is shown that neither the behaviour of double heterozygotes for sex-linked genes nor that of X-autosome translocations provides independent evidence in favour of the L.H.: in each case, the interpretation depends on that of the behaviour of single heterozygotes and hence fails to discriminate. Moreover, new facts from both types of situation are also contrary to the L.H. In particular, a unified interpretation which fits the behaviour of genes in all known types of X-autosome translocations in the mouse requires the assumption that partial inhibition of gene action happens in both X-chromosomes of mouse females, and presumably the females of other mammals. The new hypothesis is consistent with all relevant genetical facts and, like the L.H., it also accounts for dosage compensation.

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.

Threshold phenomena versus cell heredity in the manifestation of sex-linked genes in mammals

Development ◽  
1969 ◽  
Vol 22 (2) ◽  
pp. 145-179
Author(s):  
Hans Grüneberg
Keyword(s):  
X Chromosome ◽  
Mode Of Action ◽  
The Other ◽  
Cell Lineages ◽  
Threshold Phenomena ◽  
The Subject ◽  
Lyon Hypothesis ◽  
Mammalian Female

The mode of action of sex-linked genes in mammals has been the subject of much discussion in recent years. This has centred round the concept that in the mammalian female, either the maternal or the paternal X-chromosome is randomly and irreversibly inactivated during development, with the result that in the female, as in the male, one X-chromosome only is active in a given cell (Lyon, 1966, and earlier papers). The Lyon Hypothesis (l.h.) is based, in part, on the mottled or striped phenotypes of heterozygotes for certain sex-linked genes affecting the coat of the mouse and other mammals: these phenotypes are regarded as a mixture of clones descended from cells in which either one or the other X-chromosome has been inactivated. As Baker (1967) rightly insists, the interpretation of a pattern as clonal must be based on known cell lineages, as without such a basis one simply postulates what should be put to the test.

scholarly journals Identification of Developmentally Specific Enhancers for Tsix in the Regulation of X Chromosome Inactivation

2005 ◽  
Vol 25 (7) ◽  
pp. 2757-2769 ◽  
Author(s):  
Nicholas Stavropoulos ◽  
Rebecca K. Rowntree ◽  
Jeannie T. Lee
Keyword(s):  
X Chromosome ◽  
Regulatory Elements ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Binary Switch ◽  
Inactive X Chromosome ◽  
The Future ◽  
Hypersensitive Sites ◽  
Mammalian Female

ABSTRACT X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future inactive X chromosome, Tsix repression is required for Xist-mediated chromosome silencing. Thus, understanding the binary switch mechanism depends on ascertaining how Tsix expression is regulated. Here we have taken an unbiased approach toward identifying Tsix regulatory elements within the X chromosome inactivation center. First, we defined the major Tsix promoter and found that it cannot fully recapitulate the developmental dynamics of Tsix expression, indicating a requirement for additional regulatory elements. We then delineated two enhancers, one classical enhancer mapping upstream of Tsix and a bipartite enhancer that flanks the major Tsix promoter. These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer. Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression. Characterization of these enhancers will facilitate the identification of trans-acting regulatory factors for X chromosome counting and choice.

Sign in / Sign up

Export Citation Format

Share Document