scholarly journals X chromosome activity in female germ cells of mice heterozygous for Searle's translocation T(X;16)16H

1981 ◽  
Vol 37 (3) ◽  
pp. 317-322 ◽  
Author(s):  
P. G. Johnston

SUMMARYThe expression of X-linked phosphoglycerate kinase (PGK-1) in germ cells from embryos heterozygous for both PGK-1 and Searle's translocation T(X; 16) 16H was examined to investigate X chromosome activity during oogenesis. The Pgk-lb allele on the translocated X chromosome was the only allele active in somatic cells of all embryos and in germ cells from 12·5 d.p.c. embryos. However, an additional faint band representing Pgk-la activity was observed in germ cells from older embryos (13·5–18·5 d.p.c.) and neonates (1–2 d.p.p.). It is concluded that there is a period when only one X chromosome is active in early female germ cells and that reactivation of the inactive X chromosome takes place just prior to meiotic prophase.

Mammals are thought to have a type of dosage compensation not so far known in any other animal group: however many X chromosomes are present, only one remains genetically active in somatic cells. Considerable evidence for this idea exists, in spite of criticism; the greatest difficulty is presented by the abnormalities in human individuals with X chromosome aberrations. Possible explanations for these abnormalities include: wrong X chromosome dosage in early development before X inactivation, reversal of inactivation, partial inactivation of both X chromosomes, activity of the X while in the condensed inactive state, and the presence of a homologous non-inactivated region of the human X and Y. In female germ cells X inactivation apparently does not occur, but the situation in male germ cells is less clear. The Y chromosome is probably also inactive in somatic cells of adults, but again its function in germ cells is not yet clear. Some species have a presumed doubly inactive X chromosome region, as well as the singly active one. The origins and functions of this region are unknown; it may have a role in female germ cells.


Development ◽  
1981 ◽  
Vol 64 (1) ◽  
pp. 251-258
Author(s):  
Andy McMahon ◽  
Mandy Fosten ◽  
Marilyn Monk

The pattern of expression of the two X chromosomes was investigated in pre-meiotic germ cells from 12½-day-old female embryos heterozygous for the variant electrophoretic forms of the X-linked enzyme phosphoglycerate kinase (PGK-1). If such germ cells carry the preferentially active Searle's translocated X chromosome (Lyon, Searle, Ford & Ohno, 1964), then only the Pgk-1 allele on this chromosome is expressed. This confirms Johnston's evidence (1979,1981) that Pgk-1 expression reflects a single active X chromosome at this time. Extracts of 12½-day germ cells from heterozygous females carrying two normal X chromosomes show both the A and the B forms of PGK; since only one X chromosome in each cell is active, different alleles must be expressed in different cells, suggesting that X-chromosome inactivation is normally random in the germ line. This result makes it unlikely that germ cells are derived from the yolk-sac endoderm where the paternally derived X chromosome is preferentially inactivated. In their pattern of X-chromosome inactivation, germ cells evidently resemble other tissues derived from the epiblast.


1988 ◽  
Vol 8 (11) ◽  
pp. 4692-4699
Author(s):  
R S Hansen ◽  
N A Ellis ◽  
S M Gartler

X8/6T2, a hamster-human hybrid cell line which contains an inactive human X chromosome, was treated with 5-azacytidine and selected for derepression of hypoxanthine-guanine phosphoribosyltransferase. Clones were examined for coreactivation of the phosphoglycerate kinase gene (Pgk). Of 68 of these hybrids, approximately 20% expressed measurable human phosphoglycerate kinase (PGK) activity. A 600-base-pair region of the Pgk 5' CpG cluster was examined for the methylation status of eight CCGG sites (site 1 being 5'-most) in a number of PGK-negative and PGK-positive cell lines. The inactive X chromosome is normally methylated at all eight sites, and this was also true for the majority of X8/6T2 cells. However, several PGK-negative hybrids were demethylated in the site 3 to site 6 region. PGK activity correlated with demethylation at both sites 6 and 7. The data for PGK-positive and -negative hybrids indicate that demethylation at or near site 7 was necessary for reactivation of Pgk. Chromatin sensitivity to MspI digestion in the nuclei of male lymphoblastoid cells and several PGK-positive and PGK-negative hybrids was examined. PGK-positive cell lines were hypersensitive to digestion, while PGK-negative hybrids were resistant. Cleavage at sites 6 and 7 was observed in all PGK-positive cell lines at each MspI concentration examined. Sites 7 and 8 were less accessible to digestion than site 6. Cleavage in the site 2 to site 5 region was observable at the lowest MspI concentration. In most PGK-positive hybrids, a nonspecific endogenous nuclease detected the presence of a hypersensitive region spanning at least 450 base pairs, bounded at the 3' end near HpaII site 6. Nuclease hypersensitivity appears to be related to promoter activity, because sites 7 and 8 are in transcribed regions of the gene. These data indicate that specific sites within the CpG cluster have a dominant controlling influence over the Pgk promoter conformation and the transcriptional activation of Pgk.


2019 ◽  
Author(s):  
Anna Mallol ◽  
Maria Guirola ◽  
Bernhard Payer

ABSTRACTIn order to prepare the genome for gametogenesis, primordial germ cells (PGCs) undergo extensive epigenetic reprogramming during migration towards the gonads in mammalian embryos. This includes changes on a genome-wide scale and additionally in females the remodeling of the inactive X-chromosome to enable X-chromosome reactivation (XCR). However, if global and X-chromosomal remodeling are related and which factors are important is unknown. Here we identify the germ cell determinant PR-domain containing protein 14 (PRDM14) as the first known factor that is instrumental for both global and X-chromosomal reprogramming in migrating mouse PGCs. We find that global upregulation of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark is PRDM14 dosage-dependent in PGCs of both sexes. When focusing on XCR, we observed that PRDM14 is required for removal of H3K27me3 from the inactive X-chromosome. Furthermore we show that global and X-chromosomal H3K27me3 reprogramming are functionally separable, despite their common regulation by PRDM14. Thereby we provide mechanistic insight and spatiotemporal resolution to the remodeling of the epigenome during mouse PGC migration and link epigenetic reprogramming to its developmental context in vivo.


Development ◽  
1967 ◽  
Vol 17 (1) ◽  
pp. 139-145
Author(s):  
J. M. Ioannou

It is widely accepted that oogenesis normally stops early in mammalian development (see Brambell, 1956; Franchi, Mandl & Zuckerman, 1962). Nevertheless, it has been claimed that mitotically active oogonia, and oocytes in early stages of meiotic prophase occur in mature specimens of Galago senegalensis (Gérard, 1920, 1932; Gérard & Herlant, 1953; Herlant, 1961; Petter-Rousseaux, 1962; Butler, 1964), G. crassicaudatus (Gérard & Herlant, 1953), G. demidoffi (Gérard, 1932; Gérard & Herlant, 1953; Petter-Rousseaux, 1962), Perodicticus potto (Gérard & Herlant, 1953), Loris tardigradus lydekkerianus (Rao, 1927; Brambell, 1930), and Daubentonia madagascariensis (Petter-Rousseaux & Bourlière, 1965). The latter is a lemuroid prosimian, while all the others are lorisoids (Hill, 1953). It has also been asserted that new germ cells are formed by direct transformation from the somatic cells of the ovarian germinal epithelium (Gérard, 1920, 1932; Rao, 1927; Gérard & Herlant, 1953).


1988 ◽  
Vol 8 (11) ◽  
pp. 4692-4699 ◽  
Author(s):  
R S Hansen ◽  
N A Ellis ◽  
S M Gartler

X8/6T2, a hamster-human hybrid cell line which contains an inactive human X chromosome, was treated with 5-azacytidine and selected for derepression of hypoxanthine-guanine phosphoribosyltransferase. Clones were examined for coreactivation of the phosphoglycerate kinase gene (Pgk). Of 68 of these hybrids, approximately 20% expressed measurable human phosphoglycerate kinase (PGK) activity. A 600-base-pair region of the Pgk 5' CpG cluster was examined for the methylation status of eight CCGG sites (site 1 being 5'-most) in a number of PGK-negative and PGK-positive cell lines. The inactive X chromosome is normally methylated at all eight sites, and this was also true for the majority of X8/6T2 cells. However, several PGK-negative hybrids were demethylated in the site 3 to site 6 region. PGK activity correlated with demethylation at both sites 6 and 7. The data for PGK-positive and -negative hybrids indicate that demethylation at or near site 7 was necessary for reactivation of Pgk. Chromatin sensitivity to MspI digestion in the nuclei of male lymphoblastoid cells and several PGK-positive and PGK-negative hybrids was examined. PGK-positive cell lines were hypersensitive to digestion, while PGK-negative hybrids were resistant. Cleavage at sites 6 and 7 was observed in all PGK-positive cell lines at each MspI concentration examined. Sites 7 and 8 were less accessible to digestion than site 6. Cleavage in the site 2 to site 5 region was observable at the lowest MspI concentration. In most PGK-positive hybrids, a nonspecific endogenous nuclease detected the presence of a hypersensitive region spanning at least 450 base pairs, bounded at the 3' end near HpaII site 6. Nuclease hypersensitivity appears to be related to promoter activity, because sites 7 and 8 are in transcribed regions of the gene. These data indicate that specific sites within the CpG cluster have a dominant controlling influence over the Pgk promoter conformation and the transcriptional activation of Pgk.


1986 ◽  
Vol 6 (11) ◽  
pp. 4122-4125 ◽  
Author(s):  
D H Keith ◽  
J Singer-Sam ◽  
A D Riggs

The 5' control region and first exon for human X-chromosome-linked phosphoglycerate kinase is contained in a G + C-rich island. We measured methylation at all HpaII sites in this 5' region of leukocyte DNA. By use of a blotting procedure that allows analysis of small DNA fragments, we found that the HpaII sites are entirely methylated when from an inactive X chromosome and entirely unmethylated when from an active one. In contrast, methylation of HpaII sites in more downstream regions of the gene is essentially the same in active and inactive X chromosomes.


1986 ◽  
Vol 6 (11) ◽  
pp. 4122-4125
Author(s):  
D H Keith ◽  
J Singer-Sam ◽  
A D Riggs

The 5' control region and first exon for human X-chromosome-linked phosphoglycerate kinase is contained in a G + C-rich island. We measured methylation at all HpaII sites in this 5' region of leukocyte DNA. By use of a blotting procedure that allows analysis of small DNA fragments, we found that the HpaII sites are entirely methylated when from an inactive X chromosome and entirely unmethylated when from an active one. In contrast, methylation of HpaII sites in more downstream regions of the gene is essentially the same in active and inactive X chromosomes.


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