UC Merced

The precise regulation of transcription governs embryonic development and adult tissue 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. DNA methyltransferase-1 (DNMT1) forms a complex with DNA methyltransferase-1-associated protein (DMAP1), which is one important component in maintaining mammalian DNA methylation, forming a repressive transcription complex. The subunit of this complex DMAP1 is a versatile protein implicated in 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 propose utilizing planarian flatworms that possess remarkable regenerative capabilities driven by pluripotent stem cells called neoblast. Our findings demonstrate an evolutionarily conserved ortholog 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 polarity markers. Our findings provide a simplified paradigm for studying DMAP1’s epigenetic regulation in adult tissues.