The DNA Methyltransferase DMAP1 is Required for Tissue Maintenance and Planarian Regeneration

Abstract

The precise regulation of transcription is required for embryonic development, adult tissue turnover, and regeneration. Epigenetic modifications play a crucial role in orchestrating and regulating the transcription of genes. These modifications are important in the transition of pluripotent stem cells and their progeny. Methylation, a key epigenetic modification, influences gene expression through changes in histone tails and direct DNA methylation. Work in different organisms has shown that the DNA methyltransferase-1-associated protein (DMAP1) may associate with other molecules to repress transcription through DNA methylation. Thus, DMAP1 is a versatile protein implicated in a myriad of events, including pluripotency maintenance, DNA damage repair, and tumor suppression. While DMAP1 has been extensively studied in vitro, its complex regulation in the context of the adult organism remains unclear. To gain insights into the possible roles of DMAP1 at the organismal level, we used planarian flatworms that possess remarkable regenerative capabilities driven by pluripotent stem cells called neoblast. Our findings demonstrate the evolutionary conservation of DMAP1 in the planarian Schmidtea mediterranea. Functional disruption of DMAP1 through RNA interference revealed its critical role in tissue maintenance, neoblast differentiation, and regeneration in S. mediterranea. Moreover, our analysis unveiled a novel function for DMAP1 in regulating cell death in response to DNA damage and influencing the expression of axial polarity markers. Our findings provide a simplified paradigm for studying DMAP1s epigenetic regulation in adult tissues. HighlightsO_LIEpigenetic regulation through DMAP1 is evolutionarily conserved in Schmidtea mediterranea and is crucial for tissue maintenance and regeneration. C_LIO_LINeoblast differentiation into epithelial, muscle, digestive, and neural fate requires DMAP1. C_LIO_LIDMAP1 regulates DNA stability and cell death during adult cell turnover. C_LIO_LIDMAP1 regulates the spatial expression of axial polarity markers in S. mediterranea. C_LI