Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells
| Autor: | Alvina G. Lai, A. Aziz Aboobaker, Prasad Abnave, Damian Kao, Samantha Jane Hughes, Farah Jaber-Hijazi, Nobuyoshi Kosaka, Yuliana Mihaylova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
Science Neurogenesis Article Epigenesis Genetic Evolution Molecular 03 medical and health sciences 0302 clinical medicine Animals Regeneration Epigenetics lcsh:Science Induced pluripotent stem cell Gene Loss function 030304 developmental biology 0303 health sciences biology Tumor Suppressor Proteins Oncogenes Planarians biology.organism_classification Cell biology Planarian 030220 oncology & carcinogenesis Histone methyltransferase Histone Methyltransferases lcsh:Q Stem cell Developmental biology |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018) |
| ISSN: | 2041-1723 |
| Popis: | 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. The Mll3/4 histone methyltransferases can act as tumour suppressors in humans. Here, the authors identify three orthologs of mammalian MLL3/4 in the planarian Schmidtea mediterranea and show that knockdown causes outgrowths in regenerating animals, suggesting that the tumour suppressive function of these genes is deeply conserved. |
| Databáze: | OpenAIRE |
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