Sex chromosome inactivation in germ cells

Mammalian sex chromosomes are an excellent model system to understand the pivotal roles of epigenetic programming in development. Sex chromosomes precisely recapitulate stereotypical epigenetic programming in a timely and spatially-coordinated manner. In females, one of the X chromosomes is inactivated for dosage compensation of X-linked genes. In males, sex chromosomes are inactivated from meiosis to spermiogenesis in a process that is essential for germ cell developments. Meiotic sex chromosomes provide a unique opportunity which enable us to dissect the process of epigenetic programming. Following the initiation of meiotic sex chromosome inactivation, various epigenetic modifications are established gradually on the sex chromosomes in a coordinated manner. Such epigenetic modifications on the sex chromosomes are maintained through meiotic cell division into the spermatids, implying the inheritance of an epigenetic memory following meiosis. We investigate the underlying mechanism of sex chromosome inactivation specifically focusing the roles of DNA damage response pathways.

Figure 1 - Initiation mechanism of meiotic sex chromosome inactivation. (A) Schematic of sex chromosome inactivation. (B) MDC1 directs chromosome-wide spreading of gH2AX. Immunostaining of meiotic chromosome spreads using antibodies against gH2AX together with the anti-SCP3 antibody. SCP3 staining displays the status of chromosome synapsis and is used to distinguish meiotic stages. Areas surrounding sex chromosomes are highlighted in dotted rectangles and magnified in the right panels. (C) Pictorial representation about the role of MDC1 in MSCI. The first step is MDC1-independent recognition of the unsynapsed axis. The second step is MDC1-dependent spreading of gH2AX to the chromosome-wide domain. Ichijima et al Genes Dev 2011 25: 959-971 Figure 1 - Initiation mechanism of meiotic sex chromosome inactivation. (A) Schematic of sex chromosome inactivation. (B) MDC1 directs chromosome-wide spreading of gH2AX. Immunostaining of meiotic chromosome spreads using antibodies against gH2AX together with the anti-SCP3 antibody. SCP3 staining displays the status of chromosome synapsis and is used to distinguish meiotic stages. Areas surrounding sex chromosomes are highlighted in dotted rectangles and magnified in the right panels. (C) Pictorial representation about the role of MDC1 in MSCI. The first step is MDC1-independent recognition of the unsynapsed axis. The second step is MDC1-dependent spreading of gH2AX to the chromosome-wide domain. Ichijima et al Genes Dev 2011 25: 959-971