Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development.

Dnmt3a and Dnmt3b, which are known as functional de novo methyltransferases, are responsible for creating genomic methylation patterns during mammalian development. Recently, we have shown that specific expression of Dnmt3b in epiblast, embryonic ectoderm, hematopoietic progenitor cells and spermatogonia cells is followed by Dnmt3a expression (Watanabe D, Suetake I, Tada T, Tajima S (2002) Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev 118:187-190; Watanabe D, Suetake I, Tajima S, Hanaoka K (2004) Expression of Dnmt3b in mouse hematopoietic progenitor cells and spermatogonia at specific stages. Gene Expr Patterns 5:43-49). In this study, we analyzed the expression of mouse de novo methyltransferases during development of the nervous systems. In the embryonic olfactory epithelium (OE), Dnmt3b was specifically expressed in Mash1 positive globose basal cells (i.e. transiently amplifying neural progenitor cells), while Dnmt3a was expressed in immature olfactory receptor neurons. Dnmt3b-positive cells were rarely observed in the adult OE, but were increased in regenerating OE with intranasal ZnSO(4) administration. Dnmt3b was also detected in the E8.5 neural plate, E10.5 spinal cord and retina cells, while Dnmt3a was expressed in postmitotic young neurons. Furthermore, Dnmt3b was specifically expressed in ES cells, while Dnmt3a was transiently expressed during neural cell differentiation of ES cells. Dnmt3b is specifically expressed in progenitor cells during hematopoiesis, spermatogenesis and neurogenesis, suggesting an important role in the initial steps of progenitor cell differentiation. Dnmt3a is expressed in postmitotic young neurons following the Dnmt3b expression. Dnmt3a may be required for the establishment of tissue-specific methylation patterns of the genome. The coordinated expression of de novo methyltransferases from Dnmt3b to Dnmt3a suggests conserved mechanisms of de novo methylation of the genome and different functions for Dnmt3b and Dnmt3a during progenitor cell development.