Loss of the histone chaperone ASF1B reduces female reproductive capacity in mice

摘要

Anti-silencing function 1 (ASF1) is an evolutionarily conserved histone H3–H4 chaperone involved in the assembly/disassembly ofnucleosome and histone modifcation. Two paralogous genes, Asf1a and Asf1b, exist in the mouse genome. Asf1a is ubiquitouslyexpressed and its loss causes embryonic lethality. Conversely, Asf1b expression is more restricted and has been less studied. Todetermine the in vivo function of Asf1b, we generated a Asf1b-defcient mouse line (Asf1bGT(ROSA-bgeo)437) in which expression of thelacZ reporter gene is driven by the Asf1b promoter. Analysis of b-galactosidase activity at early embryonic stages indicated acorrelation between Asf1b expression and cell differentiation potential. In the gonads of both male and female, Asf1b expression wasspecifcally detected in the germ cell lineage with a peak expression correlated with meiosis. The viability of Asf1b-null mice suggeststhat Asf1b is dispensable for mouse development. However, these mice showed reduced reproductive capacity compared withwild-type controls. We present evidence that the timing of meiotic entry and the subsequent gonad development are affected moreseverely in Asf1b-null female mice than in male mice. In female mice, in addition to subfertility related to altered gamete formation,variable defects compromising the development and/or survival of their offspring were also observed. Altogether, our data indicatethe importance of Asf1b expression at the time of meiotic entry, suggesting that chromatin modifcations may play a central role inthis process.