Meiotic Pairing of Homologous Chromosomes and Silencing of Heterologous Regions

Abstract

In meiotic prophase, homologous chromosomes pair and recombine, which ensures correct segregation of the homologs at the metaphase to anaphase transition of the first meiotic division. As a first step, early in meiotic prophase, DNA double-strand breaks (DSBs) are introduced by SPO11 at hundreds of sites throughout the genome. In mammals, formation and repair of these breaks is essential for the pairing process. The sex chromosomes, X and Y, are largely heterologous and pair only in the small pseudoautosomal homologous regions. The large heterologous regions show delayed repair of DSBs and asynapsis, which triggers meiotic sex chromosome inactivation (MSCI), leading to the formation of the transcriptionally silenced XY body. Initiation of XY body formation is known to require phosphorylation of H2AX, which is also associated with damage-induced DSB repair in somatic cells. MSCI is considered as a specialized form of a general meiotic silencing mechanism that also silences autosomal unsynapsed chromatin during male and female meiotic prophase: meiotic silencing of unsynapsed chromatin (MSUC). Whereas the XY pair remains always largely unsynapsed and inactivated, autosomal nonhomologous regions frequently show heterologous synapsis and escape from inactivation. Hence, MSUC is less efficient than MSCI. However, if MSUC occurs, MSCI is incomplete, indicating that the two mechanisms are functionally interacting. Herein, we briefly review how X and Y evolved from a pair of autosomes, in relation to X-chromosomal dosage compensation in females and MSCI in males. Next, we describe current ideas about initiation and maintenance of MSCI and MSUC. We also discuss MSCI in birds, a species with female heterogamety. Insight in the mechanism of meiotic silencing is highly relevant for our understanding of male infertility associated with translocations, particularly when these occur between an autosome and the X. Furthermore, we anticipate that dysregulation of MSCI may impact on early embryonic development.