Methylation profiles of DXPas34 during the onset of X-inactivation

Prissette, Marine; El‐Maarri, Osman; Arnaud, Danielle; Walter, Jörn; Avner, Philip

doi:10.1093/hmg/10.1.31

Cited by 52 publications

(35 citation statements)

References 29 publications

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“…Interestingly, imprinted regulation of Ascl2 operates in a methylation-independent manner (Caspary et al, 1998;Tanaka et al, 1999). The Xist gene and its antisense transcript, Tsix, also lack germline-derived methylation imprints (McDonald et al, 1998;Prissette et al, 2001). This suggests either that imprinting is disrupted through different mechanisms for distinct genes or that a uniform process upstream of methylation operates at all imprinted loci, resulting in disruptions to both imprinted gene expression and methylation.…”

Section: Discussionmentioning

confidence: 99%

Selective loss of imprinting in the placenta following preimplantation development in culture

et al. 2004

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Preimplantation development is a period of dynamic epigenetic change that begins with remodeling of egg and sperm genomes, and ends with implantation. During this time, parental-specific imprinting marks are maintained to direct appropriate imprinted gene expression. We previously demonstrated that H19 imprinting could be lost during preimplantation development under certain culture conditions. To define the lability of genomic imprints during this dynamic period and to determine whether loss of imprinting continues at later stages of development, imprinted gene expression and methylation were examined after in vitro preimplantation culture. Following culture in Whitten's medium, the normally silent paternal H19 allele was aberrantly expressed and undermethylated. However, only a subset of individual cultured blastocysts (∼65%) exhibited biallelic expression, while others maintained imprinted H19 expression. Loss of H19 imprinting persisted in mid-gestation conceptuses. Placental tissues displayed activation of the normally silent allele for H19, Ascl2, Snrpn, Peg3 and Xist while in the embryo proper imprinted expression for the most part was preserved. Loss of imprinted expression was associated with a decrease in methylation at the H19 and Snrpn imprinting control regions. These results indicate that tissues of trophectoderm origin are unable to restore genomic imprints and suggest that mechanisms that safeguard imprinting might be more robust in the embryo than in the placenta.

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Section: Discussionmentioning

confidence: 99%

Selective loss of imprinting in the placenta following preimplantation development in culture

et al. 2004

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“…Lee proposed the presence of an imprinting center within the CpG-rich domain overlapping the Tsix promoter which responds to activating maternal and repressive paternal signaling to facilitate imprinted Tsix expression (17). Analysis of the DXPas34 locus and the Tsix promoter by bisulfite sequencing revealed that methylation does not represent the imprinting mark and is also unlikely to play a role in the regulation of Tsix transcription from this site (35). However, it cannot be excluded that the imprinting is associated with a methylation-independent mechanism.…”

mentioning

confidence: 99%

Antisense Transcription through the Xist Locus Mediates Tsix Function in Embryonic Stem Cells

Luikenhuis

Wutz

Jaenisch

2001

Molecular and Cellular Biology

185

188

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Expression of the Xist gene, a key player in mammalian X inactivation, has been proposed to be controlled by the antisense Tsix transcript. Targeted deletion of the Tsix promoter encompassing the DPXas34 locus leads to nonrandom inactivation of the mutant X, but it remains unresolved whether this phenotype is caused by loss of Tsix transcription or by deletion of a crucial DNA element. In this study we determined the role of Tsix transcription in random X inactivation by using mouse embryonic stem (ES) cells as a model system. Two approaches were chosen to modulate Tsix transcription with minimal disturbance of genomic sequences. First, Tsix transcription was functionally inhibited by introducing a transcriptional stop signal into the transcribed region of Tsix. In the second approach, an inducible system for Tsix expression was created. We found that the truncation of the Tsix transcript led to complete nonrandom inactivation of the targeted X chromosome. Induction of Tsix transcription during ES cell differentiation, on the other hand, caused the targeted chromosome always to be chosen as the active chromosome. These results for the first time establish a function for antisense transcription in the regulation of X inactivation.Dosage compensation in mammals is achieved by a unique mechanism that leads to transcriptional silencing of almost all genes present on one of the two X chromosomes in female cells, a process known as X-chromosome inactivation (X inactivation) (24). In undifferentiated cells, all X chromosomes are active and X inactivation is initiated at the onset of differentiation both in vivo and in vitro (31). The number of X chromosomes that are to be inactivated is determined relative to the ploidy of the cell, and X inactivation is initiated only when the number of X chromosomes exceeds one in a diploid nucleus. Each cell then makes the epigenetic choice to keep one X chromosome active and to inactivate all supernumerary X chromosomes (the n -1 rule, with n the total number of X chromosomes in the cell, and n -1 the number of X chromosomes that are being inactivated). One model suggests the presence of a blocking factor in limited quantities that can only protect one X chromosome from inactivation per diploid set of chromosomes (2). X-chromosome choice is random in the embryonic lineage of the mouse and other mammals but is influenced by a number of epigenetic and genetic factors. In metatherian mammals, such as kangaroos (8), and in the extraembryonic tissues of some eutherian mammals, including mice (43), the paternal X chromosome is imprinted and always undergoes inactivation. In addition, the choice in embryonic tissues of mice is influenced by the X-controlling element (Xce) such that X inactivation is skewed toward the chromosome possessing the weaker Xce allele (29). It has been shown that at least four alleles exist in mice: Xce a , Xce b , Xce c , and Xce d , with Xce a being the weakest and Xce d being the strongest allele. X-autosomal translocations and transgenic studies in mice have ...

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“…2A), a possibility congruent with the imprinted status of the Xs in extraembryonic cells in which the stereotypical paternal X silencing is the rule. Although the field has yet to reach a consensus on the nature of the "imprint," differential CpG methylation within the Xist-Tsix-Xite regions has been implicated (Norris et al 1994;Ariel et al 1995;Courtier et al 1995;Zuccotti and Monk 1995;McDonald et al 1998;Prissette et al 2001;Boumil et al 2006). We note that slight differences in the methylation pattern and the lack of functional evidence thus far leave open the question of which, if any, of these marks constitute the primary imprint.…”

Section: X-chromosome Inactivation: Two Identical Substrates Two Oppmentioning

confidence: 83%

X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways

Anguera¹,

Sun²,

Xu³

et al. 2006

Cold Spring Harbor Symposia on Quantitative Biology

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Methylation profiles of DXPas34 during the onset of X-inactivation

Cited by 52 publications

References 29 publications

Selective loss of imprinting in the placenta following preimplantation development in culture

Selective loss of imprinting in the placenta following preimplantation development in culture

Antisense Transcription through the Xist Locus Mediates Tsix Function in Embryonic Stem Cells

X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways

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