Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Y. Mihaylova; P. Abnave; D. Kao; S. Hughes; A. Lai; F. Jaber-Hijazi; N. Kosaka; A.A. Aboobaker

doi:10.1038/s41467-018-06092-6

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Y. Mihaylova, P. Abnave, D. Kao, S. Hughes, A. Lai, F. Jaber-Hijazi, N. Kosaka, A.A. Aboobaker

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Abstract

© 2018, The Author(s).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.

Original language	English
Article number	3633
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06092-6
Publication status	Published - 1 Dec 2018
Externally published	Yes

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title = "Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells",

abstract = "{\textcopyright} 2018, The Author(s).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.",

author = "Y. Mihaylova and P. Abnave and D. Kao and S. Hughes and A. Lai and F. Jaber-Hijazi and N. Kosaka and A.A. Aboobaker",

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T1 - Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

AU - Mihaylova, Y.

AU - Abnave, P.

AU - Kao, D.

AU - Hughes, S.

AU - Lai, A.

AU - Jaber-Hijazi, F.

AU - Kosaka, N.

AU - Aboobaker, A.A.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - © 2018, The Author(s).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.

AB - © 2018, The Author(s).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.

U2 - 10.1038/s41467-018-06092-6

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JF - Nature Communications

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ER -

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

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