Xy body, histone

Chromosome-wide inactivation is an epigenetic signature of sex chromosomes. The mechanism by which the chromosome-wide domain is recognized and gene silencing is induced remains unclear. Here we identify an essential mechanism underlying the recognition of the chromosome-wide domain in the male germline. We show that mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX), defines the chromosome-wide domain, initiates meiotic sex chromosome inactivation (MSCI), and leads to XY body formation...

Xlr6 is a novel but uncharacterized X-linked gene that is upregulated in meiotic prophase I during mouse spermatogenesis. Xlr6 belongs to the Xlr gene family, which includes a component of the axial/lateral element of the synaptonemal complex, Sycp3, and its transcripts are abundant in the fetal ovary and adult testis. Immunostaining and Western blot analysis demonstrate a diffuse localization pattern for this protein in the nucleus and an association with chromatin during the leptotene and zygotene stages...

Less than 2% of the 80-90% heritability of major psychiatric disease, for example, schizophrenia and manic-depressive illness is attributable to genes identified by linkage and association. Where is the missing heritability? The recently described PRDM9 gene imposes epigenetic stability on the XY body in male meiosis including Sapiens-specific variation relating to a gene pair (Protocadherin11XY) created by X to Y duplication at 6MYA. Thus sexually dimorphic variation that distinguishes the species may be transmitted between generations in epigenetic form that evades detection by linkage and association...

Pairing of the sex chromosomes during mammalian meiosis is characterized by the formation of a unique heterochromatin structure at the XY body. The mechanisms underlying the formation of this nuclear domain are reportedly highly conserved from marsupials to mammals. In this study, we demonstrate that in contrast to all eutherian species studied to date, partial synapsis of the heterologous sex chromosomes during pachytene stage in the horse is not associated with the formation of a typical macrochromatin domain at the XY body...

In many animals and some fungi, mechanisms have been described that target unpaired chromosomes and chromosomal regions for silencing during meiotic prophase. These phenomena, collectively called "meiotic silencing," target sex chromosomes in the heterogametic sex, for example, the X chromosome in male nematodes and the XY-body in male mice, and also target any other chromosomes that fail to synapse due to mutation or chromosomal rearrangement. Meiotic silencing phenomena are hypothesized to maintain genome integrity and perhaps function in setting up epigenetic control of embryogenesis...

BACKGROUND: The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin modifications and their effects on global gene expression patterns, in spermatocytes and spermatids. RESULTS: HR6B is enriched on the XY body and on centromeric regions in pachytene spermatocytes...

During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW), whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase...

OBJECTIVE: To study the meiotic abnormalities during prophase I in an azoospermic man with t(1;21) reciprocal translocation. DESIGN: Analysis of synapses, recombination, and transcription inactivation in a testicular biopsy sample. SETTING: Research laboratory. PATIENT(S): One azoospermic patient with t(1;21) and five men with normal spermatogenesis. INTERVENTION(S): Immunostaining for SCP3, MLH1, and gamma-H2AX/BRCA1 was performed on biopsy to identify synapses, recombination, and transcriptional inactivation, respectively...

Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase. We rescued infertility in male hybrids with bacterial artificial chromosomes carrying Prdm9 from a strain with the "fertility" Hst1(f) allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize gammaH2AX into the pachynema sex (XY) body...

SUMO-1, a ubiquitin-like protein, is covalently bound to many proteins, leading to chromatin inactivation and transcriptional repression. The high concentration of SUMO-1 on the XY body in rodents suggests that this protein has an important role in facultative heterochromatin organization. In human, the precise role of SUMO in chromatin/heterochromatin organization remains to be defined. Here we describe the SUMO-1 distribution, during human male meiosis, in relation to the formation of the different types of heterochromatin...

A reciprocal translocation between the q arm of the Y chromosome and the q arm of chromosome 14 was identified in a young, phenotypically normal boar presenting azoospermia. Testicular biopsies were analyzed by classical histological and immunolocalization techniques, and by fluorescence in situ hybridization. Meiotic pairing analysis of 85 pachytene spreads showed the presence of an open structure corresponding to a quadrivalent formed by chromosomes 14, X, and the derivative chromosomes 14 and Y in 84.7% of the cases...

Although X inactivation is thought to balance gene expression between the sexes, some genes escape inactivation, potentially contributing to differences between males and females. Utx (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome) is an escapee gene that encodes a demethylase specific for lysine 27 of histone H3, a mark of repressed chromatin. We found Utx to be expressed higher in females than in males in developing and adult brains and in adult liver. XX mice had a higher level of Utx than XY mice, regardless of whether they had testes or ovaries, indicating that the sexually dimorphic gene expression was a consequence of the sex chromosome complement...

A gene for FK506 binding protein 6 (Fkbp6) expresses during a specific stage of male and female meiosis. Disruption of the gene influences male reproduction, i.e. arrests spermatogenesis, but not female reproduction. Using the mouse model (targeted disruption), the role of the gene in homologous chromosome pairing has been demonstrated in a previous study. For further understanding the function of Fkbp6 in chromosome synapsis, we evaluated chromosome pairings during male meiosis in the as/as rat, a spontaneous null mutation, and compared them with those of the mouse model...

It is now estimated that 150-200 genes clustered in several discrete regions escape X inactivation in somatic cells of human females by unknown mechanisms. Here, we show that although the human female inactive X chromosome is largely devoid of histone 3 lysine 4 trimethylation (H3K4me3), regions that are known to escape X inactivation, including the pseudoautosomal regions, are enriched with this modification. Also, H3K4me3, unlike H3K4me2 and H4 and H3 acetylation, is restricted to discrete regions on metaphase chromosomes...

The meiotic sex chromosomes of the American marsupials Monodelphis dimidiata and Didelphis albiventris were studied with electron microscopy (EM) and with immunofluorescence localization of meiotic proteins SYCP1 and SYCP3, and proteins essential for meiotic sex chromosome inactivation (MSCI), gamma-H2AX and BRCA1. The chromatin of the non-synaptic X and Y chromosomes contains gamma-H2AX, first as foci and then as homogeneous staining at late stages. The thick and split X and Y axes are labelled with BRCA1 except at one terminus...

Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC)...

Mono-ubiquitylated H2A marks the transcriptionally silenced XY body during male meiotic prophase. Concomitant with H2A(K119ub1), the ubiquitin-conjugating enzyme HR6B is also enriched on the XY body. We analyzed H2A and H2B ubiquitylation in Hr6b-knockout mouse spermatocytes, but no global changes were detected. Next, we analyzed phosphorylation of the threonine residues T120 and T119 that are adjacent to the K119 and K120 target sites for ubiquitylation in H2A and H2B, respectively. In wild-type cells, H2A(T120ph) and H2B(T119ph) mark meiotically unpaired and silenced chromatin, including the XY body...

Gametogenesis is a sexually dimorphic process requiring profound differences in germ cell differentiation between the sexes. In mammals, the presence of heteromorphic sex chromosomes in males creates additional sex-specific challenges, including incomplete X and Y pairing during meiotic prophase. This triggers formation of a heterochromatin domain, the XY body. The XY body disassembles after prophase, but specialized sex chromatin persists, with further modification, through meiosis. Here, we investigate the function of DMRT7, a mammal-specific protein related to the invertebrate sexual regulators Doublesex and MAB-3...

The product of the Scmh1 gene, a mammalian homolog of Drosophila Sex comb on midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1). We have identified Scmh1 as an indispensable component of the Prc1. During progression through pachytene, Scmh1 was shown to be excluded from the XY body at late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110 (Pcgf2), Bmi1 and Cbx2. We have identified the role of Scmh1 in mediating the survival of late pachytene spermatocytes...

BACKGROUND: The close apposition of multivalents with the XY body has been repeatedly described in heterozygous carriers of chromosomal rearrangements. Because in many of these carriers spermatogenesis is deeply disturbed at the spermatocyte level, the association of autosomal chromatin with the XY body may impair the spermatocyte life. METHODS: Testicular biopsies from three men carriers of three different chromosomal rearrangements have been analysed by electron microscopy (EM) and immunolocalization of meiotic proteins...