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BMC Genomics

, 16:291

First Online: 12 April 2015Received: 12 December 2014Accepted: 30 March 2015DOI: 10.1186-s12864-015-1501-9

Cite this article as: Federici, F., Mulugeta, E., Schoenmakers, S. et al. BMC Genomics 2015 16: 291. doi:10.1186-s12864-015-1501-9


BackgroundIn mammalian meiotic prophase, homologous chromosome recognition is aided by formation and repair of programmed DNA double-strand breaks DSBs. Subsequently, stable associations form through homologous chromosome synapsis. In male mouse meiosis, the largely heterologous X and Y chromosomes synapse only in their short pseudoautosomal regions PARs, and DSBs persist along the unsynapsed non-homologous arms of these sex chromosomes. Asynapsis of these arms and the persistent DSBs then trigger transcriptional silencing through meiotic sex chromosome inactivation MSCI, resulting in formation of the XY body. This inactive state is partially maintained in post-meiotic haploid spermatids postmeiotic sex chromatin repression, PSCR. For the human, establishment of MSCI and PSCR have also been reported, but X-linked gene silencing appears to be more variable compared to mouse. To gain more insight into the regulation and significance of MSCI and PSCR among different eutherian species, we have performed a global analysis of XY pairing dynamics, DSB repair, MSCI and PSCR in the domestic dog Canis lupus familiaris, for which the complete genome sequence has recently become available, allowing a thorough comparative analyses.

ResultsIn addition to PAR synapsis between X and Y, we observed extensive self-synapsis of part of the dog X chromosome, and rapid loss of known markers of DSB repair from that part of the X. Sequencing of RNA from purified spermatocytes and spermatids revealed establishment of MSCI. However, the self-synapsing region of the X displayed higher X-linked gene expression compared to the unsynapsed area in spermatocytes, and was post-meiotically reactivated in spermatids. In contrast, genes in the PAR, which are expected to escape MSCI, were expressed at very low levels in both spermatocytes and spermatids. Our comparative analysis was then used to identify two X-linked genes that may escape MSCI in spermatocytes, and 21 that are specifically re-activated in spermatids of human, mouse and dog.

ConclusionsOur data indicate that MSCI is incomplete in the dog. This may be partially explained by extensive, but transient, self-synapsis of the X chromosome, in association with rapid completion of meiotic DSB repair. In addition, our comparative analysis identifies novel candidate male fertility genes.

KeywordsMeiosis Sex chromosomes Spermatogenesis Meiotic sex chromosome inactivation Synaptonemal complex Transcriptome MSCI Dog Spermatocytes Spermatids DNA double-strand break repair AbbreviationsANCAdenine nucleotide carrier


DSBsDNA double-strand breaks


FISHFluorescent in situ hybridization

FPKMFragments Per Kilobase of transcript per Million fragments mapped

HRHomologous recombination

MSCIMeiotic Sex Chromosome Inactivation

MSUCMeiotic Silencing of Unsynapsed Chromatin

NAHRNonallelic homologous recombination

PARPseudoautosomal region

PBSPhosphate buffered saline

PSCRPostmeiotic Sex Chromatin Repression

SCSynaptonemal complex

SIMStructured illumination microscopy

Federica Federici and Eskeatnaf Mulugeta contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1501-9 contains supplementary material, which is available to authorized users.

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Autor: Federica Federici - Eskeatnaf Mulugeta - Sam Schoenmakers - Evelyne Wassenaar - Jos W Hoogerbrugge - Godfried W van der He


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