X chromosome inactivation is most commonly studied in the context of female mammalian development, where it performs an essential role in dosage compensation. However, another form of X-inactivation takes place in the male, during spermatogenesis, as germ cells enter meiosis. This second form of X-inactivation, called meiotic sex chromosome inactivation (MSCI) has emerged as a novel paradigm for studying the epigenetic regulation of gene expression. New studies have revealed that MSCI is a special example of a more general mechanism called meiotic silencing of unsynapsed chromatin (MSUC), which silences chromosomes that fail to pair with their homologous partners and, in doing so, may protect against aneuploidy in subsequent generations. Furthermore, failure in MSCI is emerging as an important etiological factor in meiotic sterility.

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Meiotic sex chromosome inactivation

The inactive X chromosome differs from the active X in a number of ways; some of these, such as allocyclic replication and altered histone acetylation, are associated with all types of epigenetic silencing, whereas others, such as DNA methylation, are of more restricted use. These features are acquired progressively by the inactive X after onset of initiation. Initiation of X-inactivation is controlled by the X-inactivation center (Xic) and influenced by the X chromosome controlling element (Xce), which causes primary nonrandom X-inactivation. Other examples of nonrandom X-inactivation are also presented in this review. The definition of a major role for Xist, a noncoding RNA, in X-inactivation has enabled investigation of the mechanism leading to establishment of the heterochromatinized X-chromosome and also of the interactions between X-inactivation and imprinting as well as between X-inactivation and developmental processes in the early embryo.

X-chromosome inactivation in mammals

Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes In Drosophila melanogaster, upregulation of the male X leads to dosage compensation It has been hypothesized that mammals likewise upregulate their active X chromosome Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos

Dosage compensation of the active X chromosome in mammals.

https://repub.eur.nl/pub/3103/eur_hoeijmakers_9027.pdf

Inactivation of the HR6B Ubiquitin-Conjugating DNA Repair Enzyme in Mice Causes Male Sterility Associated with Chromatin Modification

Postmeiotic Sex Chromatin in the Male Germline of Mice

https://repub.eur.nl/pub/3081/eur_hoeijmakers_9035.pdf

A.P.N. Themmen

Papers

Postmeiotic transcription of X and Y chromosomal genes during spermatogenesis in the mouse.