Faculty Opinions recommendation of A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation.

ABSTRACT By combining a tissue-specific microarray screen with mouse uniparental duplications, we have identified a novel imprinted gene, Dopa decarboxylase (Ddc), on chromosome 11. Ddc_exon1a is a 2-kb transcript variant that initiates from an alternative first exon in intron 1 of the canonical Ddc transcript and is paternally expressed in trabecular cardiomyocytes of the embryonic and neonatal heart. Ddc displays tight conserved linkage with the maternally expressed and methylated Grb10 gene, suggesting that these reciprocally imprinted genes may be coordinately regulated. In Dnmt3L mutant embryos that lack maternal germ line methylation imprints, we show that Ddc is overexpressed and Grb10 is silenced. Their imprinting is therefore dependent on maternal germ line methylation, but the mechanism at Ddc does not appear to involve differential methylation of the Ddc_exon1a promoter region and may instead be provided by the oocyte mark at Grb10. Our analysis of Ddc redefines the imprinted Grb10 domain on mouse proximal chromosome 11 and identifies Ddc_exon1a as the first example of a heart-specific imprinted gene.

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Major sex-determining genes and the control of sexual dimorphism in Caenorhabditis elegans

Genome ◽

10.1139/g89-116 ◽

1989 ◽

Vol 31 (2) ◽

pp. 625-637 ◽

Cited By ~ 4

Author(s):

Jonathan Hodgkin ◽

Andrew D. Chisholm ◽

Michael M. Shen

Keyword(s):

Caenorhabditis Elegans ◽

Sex Determination ◽

X Chromosome ◽

Germ Line ◽

Cell Lineage ◽

Regulatory Genes ◽

Nematode Caenorhabditis Elegans ◽

X Chromosomes ◽

The Many ◽

Lineage Analysis

Sex determination in Caenorhabditis elegans involves a cascade of major regulatory genes connecting the primary sex determining signal, X chromosome dosage, to key switch genes, which in turn direct development along either male or female pathways. Animals with one X chromosome (XO) are male, while animals with two X chromosomes (XX) are hermaphrodite: hermaphrodite development occurs because the action of the regulatory genes is modified in the germ line so that both sperm and oocytes are made inside a completely female soma. The regulatory genes are being examined by both genetic and molecular means. We discuss how these major genes, in particular the last switch gene in the cascade, tra-1, might regulate the many different sex-specific events that occur during the development of the hermaphrodite and of the male.Key words: nematode, Caenorhabditis elegans, sex determination, sexual differentiation, cell lineage analysis.

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Random X-chromosome inactivation in female primordial germ cells in the mouse

Development ◽

10.1242/dev.64.1.251 ◽

1981 ◽

Vol 64 (1) ◽

pp. 251-258

Author(s):

Andy McMahon ◽

Mandy Fosten ◽

Marilyn Monk

Keyword(s):

X Chromosome ◽

Germ Cells ◽

Germ Line ◽

Primordial Germ Cells ◽

Phosphoglycerate Kinase ◽

X Chromosome Inactivation ◽

Yolk Sac ◽

Chromosome Inactivation ◽

X Chromosomes

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.

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GENETIC ANALYSIS OF THREE DOMINANT FEMALE-STERILE MUTATIONS LOCATED ON THE X CHROMOSOME OF DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/105.2.309 ◽

1983 ◽

Vol 105 (2) ◽

pp. 309-325

Author(s):

D Busson ◽

M Gans ◽

K Komitopoulou ◽

M Masson

Keyword(s):

X Chromosome ◽

Germ Line ◽

Female Sterility ◽

Recessive Mutation ◽

Wild Type Allele ◽

Wild Type ◽

Allelic Series ◽

Type Allele ◽

Dominant Female ◽

Female Germ Line

ABSTRACT Three dominant female-sterile mutations were isolated following ethyl methanesulfonate (EMS) mutagenesis. Females heterozygous for two of these mutations show atrophy of the ovaries and produce no eggs (ovoD 1) or few eggs (ovoD 2); females heterozygous for the third mutation, ovoD 3, lay flaccid eggs. All three mutations are germ line-dependent and map to the cytological region 4D-E on the X chromosome; they represent a single allelic series. Two doses of the wild-type allele restore fertility to females carrying ovoD 3 and ovoD 2, but females carrying ovoD 1 and three doses of the wild-type allele remain sterile. The three mutations are stable in males but are capable of reversion in females; reversion of the dominant mutations is accompanied by the appearance, in the same region, of a recessive mutation causing female sterility. We discuss the utility of these mutations as markers of clones induced in the female germ line by mitotic recombination as well as the nature of the mutations.

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The H19 Differentially Methylated Region Marks the Parental Origin of a Heterologous Locus without Gametic DNA Methylation

Molecular and Cellular Biology ◽

10.1128/mcb.24.9.3588-3595.2004 ◽

2004 ◽

Vol 24 (9) ◽

pp. 3588-3595 ◽

Cited By ~ 29

Author(s):

Kye-Yoon Park ◽

Elizabeth A. Sellars ◽

Alexander Grinberg ◽

Sing-Ping Huang ◽

Karl Pfeifer

Keyword(s):

Dna Methylation ◽

Mouse Chromosome ◽

Germ Line ◽

Transcriptional Silencing ◽

Chromosome 7 ◽

Differentially Methylated Region ◽

Parental Origin ◽

Imprinted Genes ◽

Chromosome 5 ◽

The Third

ABSTRACT Igf2 and H19 are coordinately regulated imprinted genes physically linked on the distal end of mouse chromosome 7. Genetic analyses demonstrate that the differentially methylated region (DMR) upstream of the H19 gene is necessary for three distinct functions: transcriptional insulation of the maternal Igf2 allele, transcriptional silencing of paternal H19 allele, and marking of the parental origin of the two chromosomes. To test the sufficiency of the DMR for the third function, we inserted DMR at two heterologous positions in the genome, downstream of H19 and at the alpha-fetoprotein locus on chromosome 5. Our results demonstrate that the DMR alone is sufficient to act as a mark of parental origin. Moreover, this activity is not dependent on germ line differences in DMR methylation. Thus, the DMR can mark its parental origin by a mechanism independent of its own DNA methylation.

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A Single Unpaired and Transcriptionally Silenced X Chromosome Locally Precludes Checkpoint Signaling in the Caenorhabditis elegans Germ Line

Genetics ◽

10.1534/genetics.109.110338 ◽

2009 ◽

Vol 184 (3) ◽

pp. 613-628 ◽

Cited By ~ 29

Author(s):

Aimee Jaramillo-Lambert ◽

JoAnne Engebrecht

Keyword(s):

Caenorhabditis Elegans ◽

X Chromosome ◽

Germ Line ◽

Checkpoint Signaling

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The asymmetry of female meiosis reduces the frequency of inheritance of unpaired chromosomes

eLife ◽

10.7554/elife.06056 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 19

Author(s):

Daniel B Cortes ◽

Karen L McNally ◽

Paul E Mains ◽

Francis J McNally

Keyword(s):

Caenorhabditis Elegans ◽

X Chromosome ◽

High Frequency ◽

Germ Line ◽

Extra Chromosome ◽

Polar Body ◽

Contractile Ring ◽

Female Meiosis ◽

Random Segregation ◽

The Asymmetry

Trisomy, the presence of a third copy of one chromosome, is deleterious and results in inviable or defective progeny if passed through the germ line. Random segregation of an extra chromosome is predicted to result in a high frequency of trisomic offspring from a trisomic parent. Caenorhabditis elegans with trisomy of the X chromosome, however, have far fewer trisomic offspring than expected. We found that the extra X chromosome was preferentially eliminated during anaphase I of female meiosis. We utilized a mutant with a specific defect in pairing of the X chromosome as a model to investigate the apparent bias against univalent inheritance. First, univalents lagged during anaphase I and their movement was biased toward the cortex and future polar body. Second, late-lagging univalents were frequently captured by the ingressing polar body contractile ring. The asymmetry of female meiosis can thus partially correct pre-existing trisomy.

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