Abstract
Currently, little is known about the evolution of epigenetic regulation in animal stem cells. Here we demonstrate, using the planarian stem cell system to investigate the role of the COMPASS family of MLL3/4 histone methyltransferases that their function as tumor suppressors in mammalian stem cells is conserved over a long evolutionary distance. To investigate the potential conservation of a genome-wide epigenetic regulatory program in animal stem cells, we assess the effects of Mll3/4 loss of function by performing RNA-seq and ChIP-seq on the G2/M planarian stem cell population, part of which contributes to the formation of outgrowths. We find many oncogenes and tumor suppressors among the affected genes that are likely candidates for mediating MLL3/4 tumor suppression function. Our work demonstrates conservation of an important epigenetic regulatory program in animals and highlights the utility of the planarian model system for studying epigenetic regulation.
Highlights
Little is known about the evolution of epigenetic regulation in animal stem cells
Individual knockdown of Elf[5] and pim-2-like did not lead to regenerative, proliferation or outgrowth-related defects (Supplementary Figure 8). These findings suggest that the up-regulation of both pim-2-like and Elf[5] is involved in driving the LPT(RNAi) outgrowth phenotype and demonstrate the utility of our data for validating the role of MLL3/4 targets
Our study demonstrates that loss of function of the planarian LPT results in the emergence of an outgrowth phenotype characterized by differentiation and proliferation defects
Summary
Little is known about the evolution of epigenetic regulation in animal stem cells. Studies of NBs have the potential to inform us about the origins of fundamental stem cell properties that underpin metazoan evolution, such as maintenance of genome stability[9], self-renewal[7,10], pluripotency[11,12,13], differentiation[14,15,16], and migration[17] All of these are highly relevant to understanding human disease processes, those leading to cancer. Complexity in the form of tissue and cell heterogeneity, life history stage and stage of pathology make resolution of epigenetic regulatory cause and effect relationships in vivo very challenging From this perspective, planarians and their accessible NB population may be a very useful model system. LPT-Trr/MLL3/4 proteins have a role in transcriptional control via mono-methylating and/or tri-methylating H3K4 at promoters and enhancers[22,23,25,26,30,35] (Supplementary Figure 1)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call