Mouse Y-linked Zfy1 and Zfy2 are expressed during the male-specific interphase between meiosis I and meiosis II and promote the 2nd meiotic division.

Nadège Vernet,Paul S Burgoyne,Michael J Mitchell,Fanny Decarpentrie,Yasuhiro Yamauchi,Monika A Ward,Shantha K Mahadevaiah,Patricia A Hunt

doi:10.1371/journal.pgen.1004444

Abstract

Mouse Zfy1 and Zfy2 encode zinc finger transcription factors that map to the short arm of the Y chromosome (Yp). They have previously been shown to promote meiotic quality control during pachytene (Zfy1 and Zfy2) and at the first meiotic metaphase (Zfy2). However, from these previous studies additional roles for genes encoded on Yp during meiotic progression were inferred. In order to identify these genes and investigate their function in later stages of meiosis, we created three models with diminishing Yp and Zfy gene complements (but lacking the Y-long-arm). Since the Y-long-arm mediates pairing and exchange with the X via their pseudoautosomal regions (PARs) we added a minute PAR-bearing X chromosome derivative to enable formation of a sex bivalent, thus avoiding Zfy2-mediated meiotic metaphase I (MI) checkpoint responses to the unpaired (univalent) X chromosome. Using these models we obtained definitive evidence that genetic information on Yp promotes meiosis II, and by transgene addition identified Zfy1 and Zfy2 as the genes responsible. Zfy2 was substantially more effective and proved to have a much more potent transactivation domain than Zfy1. We previously established that only Zfy2 is required for the robust apoptotic elimination of MI spermatocytes in response to a univalent X; the finding that both genes potentiate meiosis II led us to ask whether there was de novo Zfy1 and Zfy2 transcription in the interphase between meiosis I and meiosis II, and this proved to be the case. X-encoded Zfx was also expressed at this stage and Zfx over-expression also potentiated meiosis II. An interphase between the meiotic divisions is male-specific and we previously hypothesised that this allows meiosis II critical X and Y gene reactivation following sex chromosome silencing in meiotic prophase. The interphase transcription and meiosis II function of Zfx, Zfy1 and Zfy2 validate this hypothesis.

Highlights

The realisation that there were spermatogenic factors on the human and mouse Y chromosomes distinct from the testis determinant came from the study of Y deletion variants [1,2]
Subsequent progress in assigning spermatogenic gene functions to mouse Yencoded genes was thwarted by a failure to disrupt Y gene functions using the emerging gene targeting techniques that had proved successful in disrupting X and autosomal gene functions, compounded by the paucity of genomic sequence data for the mouse Y chromosome
The mouse Y chromosome genes Zfy1 and Zfy2 were first identified in the late 1980s during the search for the gene on the Y that triggers male development; they encode proteins that regulate the expression of other genes to which they bind via a ‘zinc finger’ domain

Summary

Introduction

The realisation that there were spermatogenic factors on the human and mouse Y chromosomes distinct from the testis determinant came from the study of Y deletion variants [1,2]. In the context of Y genes mapping to the short arm (Yp), three XO male mouse models with diminishing Yp gene complements were utilised (Figure 1): XSxraO in which the X carries the Yp-derived sex-reversal factor Tp(Y)1CtSxr-a that provides an almost complete Yp gene complement [6], XSxrbO males where the X carries an Sxra derivative Tp(Y)1CtSxr-b in which a 1.3Mb deletion (DSxr-b) has removed the majority of the Yp gene complement [6,7], and XOSry males in which the only Yp gene present is an autosomally located Sry transgene [8] The latter two Yp-deficient models have a marked block in spermatogonial proliferation, and in 2001 we reported that this block could be circumvented by the addition of Eif2s3y; this Y-

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