During male meiotic prophase, the heterologous X and Y chromosomes synapse only in small pseudoautosomal regions. A specific mechanism, named meiotic silencing of unsynapsed chromatin (MSUC), detects the unsynapsed parts of X and Y, leading to formation of the transcriptionally silenced XY body. During postmeiotic development, genes are re-expressed from X and Y, but the paternal X is preferentially inactivated in the early embryo. Autosomal chromosomal regions that remain unpaired are also transcriptionally silenced in male and female meiotic prophase cells. We have observed specific histone modifications associated with unpaired chromosomal regions, and these are affected in mice carrying a null mutation in the gene encoding the ubiquitin-conjugating enzyme HR6B. In addition, analyses of gene expression showed specific derepression of X-linked genes in postmeiotic Hr6b knockout spermatids. At present, we are investigating the efficiency of MSUC, and we have initiated research to study possible transgenerational effects of MSUC. RAD18, a ubiquitin ligating enzyme that interacts with HR6B, also accumulates on unpaired chromosomal regions in meiotic prophase cells. We aim to unravel the identity and function of ubiquitinated chromatin components on unpaired chromosomal regions in meiotic prophase cells. In addition, we are investigating the roles of HR6B, the closely related protein Hr6a, and RAD18 in histone code dynamics and DNA repair in somatic and germ line cells.