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

Yuliana Mihaylova, Prasad Abnave, Damian Kao, Samantha Hughes, Alvina Lai, Farah Jaber-Hijazi, Nobuyoshi Kosaka, A. Aziz Aboobaker*

*Corresponding author for this work

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Article number3633
Number of pages17
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 7 Sep 2018

Fingerprint

Planarians
suppressors
Pluripotent Stem Cells
stem cells
Stem cells
Epigenomics
conservation
Tumors
Conservation
Stem Cells
tumors
animals
Animals
Neoplasms
Genes
oncogenes
COMPASS (programming language)
genome
Oncogenes
genes

Keywords

  • Adult stem cells
  • Cancer stem cells
  • Epigenetics
  • Evolutionary developmental biology

Cite this

Mihaylova, Yuliana ; Abnave, Prasad ; Kao, Damian ; Hughes, Samantha ; Lai, Alvina ; Jaber-Hijazi, Farah ; Kosaka, Nobuyoshi ; Aboobaker, A. Aziz. / Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells. In: Nature Communications. 2018 ; Vol. 9.
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Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells. / Mihaylova, Yuliana; Abnave, Prasad; Kao, Damian; Hughes, Samantha; Lai, Alvina; Jaber-Hijazi, Farah; Kosaka, Nobuyoshi; Aboobaker, A. Aziz.

In: Nature Communications, Vol. 9, 3633, 07.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Mihaylova, Yuliana

AU - Abnave, Prasad

AU - Kao, Damian

AU - Hughes, Samantha

AU - Lai, Alvina

AU - Jaber-Hijazi, Farah

AU - Kosaka, Nobuyoshi

AU - Aboobaker, A. Aziz

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AB - 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.

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KW - Cancer stem cells

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