Meiotic sex chromosome inactivation

Turner, James M. A.

doi:10.1242/dev.000018

Cited by 625 publications

(642 citation statements)

References 75 publications

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“…These chromosomes are held together during meiotic prophase by the formation of a single crossover at X-Y homologous sequences known as the pseudoautosomal region [99]. The unpaired regions of the chromosomes form a sub-domain on the nuclear periphery termed the sex body where they undergo transcriptional silencing in a process known as MSCI (meiotic sex chromosome inactivation) [100]. MSCI represents a specific instance of a common response to the existence of unpaired DNA regions during meiosis, first identified in the fungus Neurospora, known as MSUC (meiotic silencing of unpaired chromatin) [101].…”

Section: Box 2: Meiotic Sex Chromosome Inactivationmentioning

confidence: 99%

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

Gill

Erkek

Peters

2012

Current Opinion in Cell Biology

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At fertilization, fusion of two differentiated gametes forms the zygote that is capable of forming all of the varied cell lineages of an organism. It is widely thought that the acquisition of totipotency involves extensive epigenetic reprogramming of the germline state into an embryonic state. However, recent data argue that this reprogramming is incomplete and that substantial epigenetic information passes from one generation to the next. In this review we summarize the changes in chromatin states that take place during mammalian gametogenesis and examine the evidence that early mammalian embryogenesis may be affected by inheritance of epigenetic information from the parental generation.

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Section: Box 2: Meiotic Sex Chromosome Inactivationmentioning

confidence: 99%

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

Gill

Erkek

Peters

2012

Current Opinion in Cell Biology

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“…More recent studies have provided empirical support for MSCI in a variety of species, including mammals (Richler et al, 1992;Handel et al, 1994;Turner, 2007), Caenorhabditis elegans (Fong et al, 2002;Kelly et al, 2002) and D. melanogaster (Hense et al, 2007;Vibranovski et al, 2009a). However, there is currently debate regarding the extent of X-linked germline expression silencing in Drosophila and whether it occurs through the same mechanism described as MSCI in other taxa.…”

Section: Introductionmentioning

confidence: 99%

‘Escaping’ the X chromosome leads to increased gene expression in the male germline of Drosophila melanogaster

2013

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Genomic analyses of Drosophila species suggest that the X chromosome presents an unfavourable environment for the expression of genes in the male germline. A previous study in D. melanogaster used a reporter gene driven by a testis-specific promoter to show that expression was greatly reduced when the gene was inserted onto the X chromosome as compared with the autosomes. However, a limitation of this study was that only the expression regulated by a single, autosomal-derived promoter was investigated. To test for an increase in expression associated with 'escaping' the X chromosome, we analysed reporter gene expression driven by the promoters of three X-linked, testis-expressed genes (CG10920, CG12681 and CG1314) that were inserted randomly throughout the D. melanogaster genome. In all cases, insertions on the autosomes showed significantly higher expression than those on the X chromosome. Thus, even genes whose regulation has adapted to the X-chromosomal environment show increased male germline expression when relocated to an autosome. Our results provide direct experimental evidence for the suppression of X-linked gene expression in the Drosophila male germline that is independent of gene dose.

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“…The sex chromosomes remain silent throughout the rest of meiotic prophase, and only few sexlinked genes are (re)activated in postmeiotic spermatids. 2 Since long, scientists have wondered how MSCI is achieved, and what its biological significance is.…”

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confidence: 99%

“…In mouse, there also is a very strong pachytene arrest during male meiosis whenever synapsis and DSB repair are affected. 2 In addition, MSCI fails in such situations. 13 A recent series of experiments by Royo et al 5 has shown that pachytene arrest in male mice can be induced by inappropriate expression of sex-linked genes, and they identified a single Y-linked gene, named Zfy, whose expression is sufficient to induce apoptosis of pachytene spermatocytes.…”

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confidence: 99%

The X and Y chromosome in meiosis: how and why they keep silent

Heijden¹,

Eijpe²,

Baarends³

2011

Asian J Androl

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T he XX/XY sex chromosomal system of mammals, including human, challenges the chromosome pairing mechanism during male meiosis. Pairing and subsequent separation of homologous chromosomes generates haploid cells from diploid cells during the meiotic divisions. One of the basic requirements for recognition between homologous chromosomes is DNA sequence identity. Since the X and Y chromosome share little homology, their quest for each other is difficult, and has special characteristics. During the lengthy meiotic prophase, all autosomal chromosomes synapse, by forming a special protein structure called the synaptonemal complex, which connects the chromosomal axes. In contrast, the X and Y chromosome synapse only in the short homologous pseudoautosomal regions, and form the so-called XY body. 1 In this specialized chromatin area, transcription is shut down by a mechanism named meiotic sex chromosome inactivation (MSCI) (reviewed by Refs. 2 and 3). The sex chromosomes remain silent throughout the rest of meiotic prophase, and only few sexlinked genes are (re)activated in postmeiotic spermatids. 2 Since long, scientists have wondered how MSCI is achieved, and what its biological significance is.Recently, two papers 4,5 significantly increased our understanding of how and why MSCI works.So far, the only molecule that was known to be absolutely essential for initiation of MSCI was cH2AX. 6 This phosphorylated form of histone H2AX marks the XY body from its formation until diplotene in mouse. 7 In mice lacking H2AX, no XY body is formed, the sex chromosomes are not silenced and meiosis arrests at pachytene. 6 The phosphorylation of H2AX at the XY body is mediated by the checkpoint kinase ATR that can be visualized along the unsynapsed axes of X and Y from late zygotene onwards. 8 In their recent paper, Ichijima et al. 4 reveal that the phosphorylation of H2AX occurs in two phases; first, it is restricted to the chromosomal axes, then the area extends, and H2AX also becomes phosphorylated in the surrounding chromatin loops. This second phase, when cH2AX spreads, depends on a protein named mediator of DNA damage checkpoint 1 (MDC1), and this function is required for transcriptional silencing of the sex chromosomes ( Figure 1). MDC1 is a known binding partner of cH2AX, 9,10 and both proteins, as well as ATR, are well known for their role in the DNA damage response pathway in somatic cells. This pathway plays a pivotal role in sensing the presence of single-stranded DNA at stalled replication forks to allow repair as well as activation of cell cycle checkpoints. Interestingly, the authors also analyzed the role of MDC1 in somatic cells. In analogy to their observations in meiotic cells, they observed reduced amplification of ATRdependent cH2AX signals after replicative stress in the absence of MDC1, compared to control cells. They also showed that RNA polymerase II is excluded from chromatin at replication-stalled sites that are marked by ATR-and MDC1-dependent cH2AX accumulation, thereby confirming and extending the obser...

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Meiotic sex chromosome inactivation

Cited by 625 publications

References 75 publications

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

‘Escaping’ the X chromosome leads to increased gene expression in the male germline of Drosophila melanogaster

The X and Y chromosome in meiosis: how and why they keep silent

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