Biomedical subjects
M Monk
Publications and source records attributed to M Monk.
Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development.
This paper shows stage- and tissue-specific global demethylation and remethylation occurring during embryonic development. The egg genome is strikingly undermethylated and the sperm genome relatively methylated. Following a loss of genomic methylation during preimplantation development, embryonic and extraembryonic lineages are progressively and independently methylated to different final extents. Methylation continues postgastrulation and hence could be a mechanism initiating, or confirming, differential programming in the definitive germ layers. It is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome (in females). Fetal germ cell DNA is markedly undermethylated and we favour the idea that the germ lineage is set aside before the occurrence of extensive methylation of DNA in fetal precursor cells.
Methylation and the X chromosome.
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Differences in methylation on the active and inactive human X chromosomes.
Methylation of CCGG sites was examined in four regions of the X chromosome with four X-chromosome clones, three obtained by cloning random segments and one encoding a structural gene. In DNA from human peripheral blood cells unmethylated sites correlating with the inactive X chromosome were detected in the vicinity of two of the random clones and also in the vicinity of a cloned sequence of the X-linked phosphoglycerate kinase gene (PGK). The third random clone covered a region whose methylation pattern was unchanged between the active and inactive X chromosomes. Differential methylation at the sites detected appears to have no functional role in the maintenance of the inactive X chromosome since both active and inactive X chromosomes were found to be undermethylated in DNA from human lymphoblastoid cells.
Dog and cat ownership among suicides and matched controls.
In Washington County, Maryland, ownership of cats and/or dogs was compared among 48 residents who committed suicide in the years 1975-83 and 96 living controls matched to the suicides by race, sex, and date of birth. Another comparison used as controls persons of same race, sex, and age who died of causes other than suicide in the same year as the suicide. No material association between pet ownership and suicide was observed.
X-chromosome activity in female mouse embryos heterozygous for Pgk-1 and Searle's translocation, T(X; 16) 16H.
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Evidence for translation of HPRT enzyme on maternal mRNA in early mouse embryos.
This paper presents evidence that maternal mRNA is responsible for the early increase in HPRT activity in preimplantation mouse embryos. Increase of HPRT activity is demonstrable from as early as 6 h postfertilization when there is barely detectable synthesis of embryonic RNA. The increase is sensitive to cycloheximide and thus requires protein synthesis, whereas it is insensitive to alpha-amanitin and therefore independent of mRNA synthesis. These results suggest that translation of HPRT occurs on pre-existing maternal mRNA. Embryo-coded HPRT activity is detectable by the 4- to 8-cell stage when the increase in HPRT activity becomes sensitive to alpha-amanitin. The transition from maternal- to embryo-coded enzyme activity is completed by the time of compaction. At this stage there is an unexplained yet reproducible loss of HPRT activity. Other maternally-inherited enzymes show a marked degradation occurring at a similar time. It is possible that the enzyme degradation observed reflects some common mechanism directing the changeover from maternally-derived to embryonically-derived enzymes.
X-chromosome inactivation mosaicism in the three germ layers and the germ line of the mouse embryo.
Electrophoretic variant forms of the X-linked enzyme phosphoglycerate kinase (PGK-1, E.C.2,7,2,3) have been used to examine X-chromosome mosaicism in tissues from 12 1/2-day post coitum heterozygous female mouse embryos. Samples of yolk-sac endoderm, neural ectoderm, heart (mesoderm), liver (endoderm) and germ cells were analysed from each embryo. In all tissues except yolk-sac endoderm, both PGK-1 isozymes were expressed. The extent of covariance among tissues with respect to the PGK-1 isozyme contribution is consistent with all tissues being derived from the same pool of cells after X-inactivation. The covariance among tissues gives an estimate of the size of this pool (47 cells) and places the earliest time of X-inactivation in epiblast cells between 4 1/2 and 5 1/2 days post coitum. From the independent variance among tissues within an individual, the average primordial precursor pool size for the three germ layers and the germ line itself was estimated as 193 cells.
Fertile females produced by inactivation of an X chromosome of "sex-reversed' mice.
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Preferential paternal X inactivation in extraembryonic tissues of early mouse embryos.
The preferential expression of the maternal X chromosome seen in certain extraembryonic membranes of the mouse was studied by investigating the tissues from which these membranes are derived during early development. The electrophoretic variant of the X-coded enzyme PGK-1 (phosphoglycerate kinase) was used to distinguish the expression of the maternal from the paternal X chromosome in heterozygous females. Both the extraembryonic ectoderm and primary endoderm of 6 1/2-day female egg cylinders gave almost exclusive expression of the maternal form of the enzyme whereas the epiblast gave near equal expression of the two parental alleles. No paternal PGK-1 band could be detected in samples of pooled 3 1/2-day blastocysts, but after 3 or 4 days of culture in vitro a faint paternal band was seen in the resultant outgrowths. The activity of the maternal band in these latter samples had increased greatly from that of the blastocysts, consistent with preferential expression of the maternal Pgk-1 allele in the trophoblastic cells of the outgrowths, while both alleles are expressed in inner-cell-mass cells. The results strongly support the idea that non-random X-chromosome expression is due to preferential paternal X inactivation in trophectoderm (from which extraembryonic ectoderm is derived) and in primary endoderm, and not to cell selection.
A stem-line model for cellular and chromosomal differentiation in early mouse-development.
Differentiation in mouse embryo development is represented formally by means of a stem-line model in which: 1. Individual choices are structured so that only a fraction of the cells of a given population receive a signal to undergo a change of state that results in a departure from the stem line. 2. Development proceeds by a series of restrictions in potency of all the cells in the stem line. 3. The stem line harbours the germ cells. 4. The germ cells are returned to a state of totipotency by some event(s) leading to meiosis.
X-chromosome activity in the germ cells of sex-reversed mouse embryos.
Germ cells were isolated from XX ovaries and XY and XX Sex-reversed (Sxr/+) testes of mouse embryos 14-16 days post coitum, and the activity of an X-chromosome-coded enzyme, hypoxanthine phosphoribosyl transferase (HPRT), relative to an autosomal one, adenine phosphoribosyl transferase was determined. The ratio of enzyme activities in XX Sxr/+ prospermatogonia was significantly higher than that in XY prospermatogonia, up to 2-fold, suggesting that the silent X chromosome is reactivated in XX male germ cells before birth, as it is in female germ cells. The ratio was several times higher still in XX oocytes than in XX prospermatogonia, confirming that the increase in HPRT activity reported in oocytes is only partly due to an X-chromosome dosage effect.
X-chromosome activity in foetal germ cells of the mouse.
A cycle of inactivation and reactivation of one X chromosome in the female (XX) germ line is shown by analysis of gene dosage effects on activity of an X-linked enzyme. The ratio of activities of the X-linked enzyme HPRT and an autosomal enzyme APRT are determined in XX and XY germ cells from embryonic gonads from the 12th to the 17th day of pregnancy. Mitotic stages of XX and XY germ cells on the 12th day have similar HPRT:APRT ratios, but on the 13th day the ratios are significantly higher in XX than XY germ cells. As the XX germ cells enter meiosis they show a marked increase in HPRT:APRT ratio which is primarily due to a rise in X-linked HPRT activity. Comparisons are made with XO germ cells on the 12th and 14th day. On the 12th day, XO do not differ from XX and XY germ cells, suggesting that only one X chromosome is active in XX germ cells at this stage. On the 14th day, on the other hand, the HPRT:APRT ratios in XO and XY germ cells are similar but in XX germ cells the ratio is significantly higher. The twofold difference between the ratio in XX and XO germ cells suggests that by this stage both X chromosomes are active in XX germ cells. The subsequent large increase of the ratio in XX relative to XY germ cells is thought to reflect their differing cell states.
Random X-chromosome inactivation in female primordial germ cells in the mouse.
The pattern of expression of the two X chromosomes was investigated in pre-meiotic germ cells from 12 1/2-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 12 1/2-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.
Blood pressure awareness and psychological well-being in the health and nutrition examination survey.
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Psychologic status and hypertension.
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Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos.
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Biochemical studies on X-chromosome activity in preimplantation mouse embryos.
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